Peptides for the treatment of inner ear or mastoid process disorders

Abstract

SorCS2-related lipid-modified cyclic peptides, cyclic peptides, lipid-modified linear peptides, and linear peptides useful in the treatment or prevention of diseases or disorders of the ear or mastoid process.

Description

[Technical Field]

[0001] (Technical field) This invention relates to peptides for use in the treatment or prevention of diseases or disorders of the ear or mastoid process. [Background technology]

[0002] (background) Sortirin-related Vps10p domain-containing receptor 2 (SorCS2), a member of the Vps10p domain receptor family, has emerged in neuroscience due to its deep involvement in neuronal viability and function (Glerup, 2014; Glerup, 2016; Leloup, 2018; Ma, 2017; Malik, 2019; Yang, 2021). SorCS2 receptors mediate the selection and transport of various ligands and receptors crucial for neurite formation, synaptic plasticity, and axonal growth. Large-scale cohort studies have highlighted the clinical relevance of SorCS2, linking it to several neurodegenerative and psychiatric disorders, including bipolar disorder, Alzheimer's disease (AD), Huntington's disease (HD), frontotemporal dementia (FTD), depression, schizophrenia, and attention-deficit / hyperactivity disorder (ADHD) (Baum, 2008; Ollila, 2009; Christoforou, 2011; Alemany, 2015; Reitz, 2015). Furthermore, SorCS2 has been functionally associated with amyotrophic lateral sclerosis (ALS) and hemoglobin hemorrhagic disease (HD), both severe neuroproteinopathys (Mori, 2015; Ma, 2017; Salasova, 2021), and also with pain-related disorders such as neuropathic pain (Richner, 2012; Ma, 2017; Miki, 2018). In proteinopathy, SorCS2 has been shown to mislocalize to disease-related aggregates, resulting in its deficiency and accelerated disease progression.

[0003] SorCS2 has been further shown to be crucial in mediating signaling by brain-derived neurotrophic factor (BDNF), which plays a central role in neuronal survival and differentiation, as well as synaptic plasticity, through the activation of its receptor, TrkB. Dysregulation of BDNF / TrkB signaling has been shown to contribute to many pathological processes, including various neurodegenerative diseases (Glerup, 2016; Qui, 2020). BDNF promotes the activation of cAMP response element-binding protein (CREB), which is well known to improve neuronal survival, synapse formation, and growth (Glerup, 2016). A key mediator of this is the production of BDNF itself by CREB (Tao, 1998), thereby establishing a positive feedback loop. CREB activation has also been described as inducing mitochondrial biosynthesis through the upregulation of PGC1a (Wu, 2006; Kang, 2017). PGC1a is a major regulator of mitochondrial biosynthesis and function, including oxidative phosphorylation and ROS detoxification (Rius-Perez, 2020; Valle, 2005).

[0004] Recent studies have identified SorCS2 loss as a causative factor of hearing loss in spontaneously deaf mouse strains, illustrating that SorCS2 may be extremely important for maintaining cochlear morphology and function (Forge et al., 2017).

[0005] The auditory process begins when sound waves enter the outer ear, travel through the auditory canal, and reach the eardrum. The eardrum vibrates, and these vibrations are transmitted to the bones of the middle ear—the malleus, incus, and stapes. These bones amplify the sound vibrations and send them to the cochlea, a fluid-filled structure in the inner ear with a basilar membrane. When the cochlea receives an acoustic signal, a traveling wave is generated, which is first amplified by the outer hair cells (OHCs). The outer hair cells (OHCs) act as biological amplifiers / compressors and modify the signal. The cochlear basilar membrane is highly frequency-specific and tonototopic. The base of the basilar membrane responds to high frequencies, while the apex responds to low frequencies. Inner hair cells (IHCs) are responsible for sending most of the auditory signals from the cochlea to the brain for processing. IHCs convert the mechanical vibrations caused by sound waves into electrical signals. Next, these electrical signals are transmitted to spiral ganglion neurons (SGNs) via the release of neurotransmitters, which then relay the auditory information to the brain for perception and interpretation.

[0006] The most common type of hearing loss is sensorineural hearing loss, which refers to hearing loss caused by any pathology of the cochlea, auditory nerve, or central nervous system. This is different from conductive hearing loss, which occurs when sound waves cannot reach the inner ear. Sensorineural hearing loss affects more than 320 million people worldwide.

[0007] For many years, the focus of hearing loss has been on the loss of the overhead cochlea (OHC) and intrahepatic cochlea (IHC). More recently, it has been shown that changes in the cochlea can also alter the neurogenic sound-evoked output of the auditory nerve, independently of hair cell loss and changes in hearing thresholds (Kohrman et al., 2020). This form of hearing loss is called silent hearing loss (HHL), reflecting the fact that the dysfunction is not revealed by standard hearing threshold tests.

[0008] One of the most detailed-documented mechanisms of HHL is degeneration of the cochlear ribbon synapse linking IHC and SGN (cochlear synaptopathy), without hair cell loss or SGN itself. In mice, excessive acoustic exposure has been shown to cause acute and irreversible synaptic ribbon loss without damaging cochlear sensory cells (Kujawa and Liberman, 2009), and these findings have since been replicated in various mammalian species. Latent hearing loss can result from several environmental factors, most commonly noise exposure, but it can also be caused by pharmacological damage following treatment with ototoxic drugs such as cisplatin, salicylates, and various antibiotics. For example, gentamicin in doses that do not harm hair cells has been associated with IHC synapse loss (Kohrman et al., 2020).

[0009] The SorCS2 signaling pathway has been implicated in various studies on hearing loss. Strong evidence links the neurotrophin BDNF to the development and maintenance of ribbon synapses, a feature demonstrated both in vitro and in vivo. BDNF released from IHC acts on TrkB on SGN, and genetic disruption of the gene encoding this receptor leads to cochlear dysfunction (Fritzsch et al., 2004). Interestingly, evidence also suggests that salicylate treatment leads to downregulation of BDNF, thereby resulting in synaptopathy and loss of IHC (Singer et al., 2008). Consistent with this, exogenous administration of BDNF or TrkB agonist monoclonal antibodies yields beneficial effects in ex vivo cochlear models, while BDNF administration has shown beneficial effects in rodent models of hearing loss (Foster et al., 2022). A major challenge in such therapeutic interventions is getting the drug into the cochlea, but certain formulations of recombinant BDNF (OTO-413, developed by Otonomy) have shown early evidence of efficacy (potency) via intratympanic administration in rodents and humans. Furthermore, noise exposure has been shown to reduce PGC-1a expression and activity, which affects ROS detoxification and further contributes to oxidative stress in animal models of noise-induced latent hearing loss (Liu et al., 2022). PGC1a has been shown to promote lysosome biosynthesis through the regulation of TFEB (the main regulator of lysosome biosynthesis) (Ghosh, 2015; Lynch, 2020). TFEB is also thought to be involved in sensorineural hearing loss; in kanamycin and furosemide-induced degenerative SGN, the nuclear-to-cytoplasmic TFEB ratio was decreased and the later stages of the autophagy flux were impaired. After autophagy dysfunction was partially mitigated by an MTOR inhibitor that promotes TFEB transfer from the cytoplasm to the nucleus, lysosomal dysfunction was significantly alleviated, oxidative stress levels decreased, and the density of viable SGNs and auditory nerve fibers increased (Ye et al., 2019).

[0010] These data support the hypothesis that modulation of the SorCS2 pathway may provide therapeutic benefit in patients suffering from inner ear disorders.

[0011] Modulators of the SorCS2 pathway are described and evidenced to have utility as medicaments. WO2017101956 relates to linear peptides and a method for modulating phosphorylation of the Vps10 domain-containing receptors SorCS1, SorCS2, or SorCS3. WO2022029281 describes cyclic peptides and a method for modulating SorCS1, SorCS2, or SorCS3. International patent application PCT / EP2023 / 053211 (publication number WO2023152229) describes peptides and a method for modulating SorCS2.

[0012] There remains a need for the provision of medicaments useful in the treatment or prevention of diseases or disorders of the ear or mastoid process. Such medicaments may offer advantages over known approaches, for example in one or more of the following aspects: (i) in vivo efficacy (iii) pharmacokinetic properties; (iv) physicochemical properties; and / or (vii) safety profile or therapeutic index (TI) may be exhibited in one or more of the above. Summary of the Invention

[0013] Summary of the Invention Provided is a method for the treatment or prevention of a disease or disorder of the ear or mastoid process in a subject, comprising administration of a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide is:[] (i) the sequence: Chemical Formula (wherein: X2 represents P, D, Q, K, G, X3 represents I, L, A, T, V, X4 represents E or A) Lipidized cyclic peptides containing said peptides or conservatively substituted variants thereof; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of said peptide (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing said peptide or a conservatively substituted variant thereof; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing said peptides or conservatively substituted variants thereof; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of said peptide (where X2 is P, X3 is something other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing said peptides or conservatively substituted variants thereof That is the method.

[0014] Also provided are peptides or pharmaceutically acceptable salts thereof for use in the treatment or prevention of diseases or disorders of the ear or mastoid process, wherein the peptide is (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing said peptides or conservatively substituted variants thereof; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of said peptide (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing said peptide or a conservatively substituted variant thereof; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing said peptides or conservatively substituted variants thereof; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of said peptide (where X2 is P, X3 is something other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing said peptides or conservatively substituted variants thereof That is the case.

[0015] Further provided is a pharmaceutical composition for the treatment or prevention of diseases or disorders of the ear or mastoid process, comprising a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide is (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing said peptides or conservatively substituted variants thereof; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of said peptide (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing said peptide or a conservatively substituted variant thereof; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing said peptides or conservatively substituted variants thereof; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of said peptide (where X2 is P, X3 is something other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing said peptides or conservatively substituted variants thereof It is a pharmaceutical composition.

[0016] Furthermore, the use of a peptide or a pharmaceutically acceptable salt thereof in the manufacture of a pharmaceutical product for the treatment or prevention of a disease or disorder of the ear or mastoid process, wherein the peptide is (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing said peptides or conservatively substituted variants thereof; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of said peptide (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing said peptide or a conservatively substituted variant thereof; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing said peptides or conservatively substituted variants thereof; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of said peptide (where X2 is P, X3 is something other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing said peptides or conservatively substituted variants thereof That is the case. [Brief explanation of the drawing]

[0017] (Brief explanation of the drawing) [Figure 1] Figures 1A-1C: Purification and qualitative check of CLP1: HPLC chromatogram (Figure 1A), LC-MS chromatogram (Figure 1B), and full-scan acquired positive ion mode spectrum (Figure 1C) of CLP1 with UV detection at 220 nm. [Figure 2] Figures 2A and 2B: CLP1 increases levels of CREB transcriptional targets: 1 μM peptide CLP1 significantly increased levels of CREB downstream targets: neurotrophic factor BDNF (Figure 2A) and mitochondrial master regulator PGC1a (Figure 2B) in primary mouse neurons at 16 and 24 hours. Peptide CPX showed no effect at these time points. Mean ± SEM. [Figure 3] Figures 3A and 3B: CLP1 removes soluble mutant HTT from Huntington's disease patient-derived fibroblasts (GM04719): Peptides CLP1 and CPX significantly reduced mutant huntingtin (mHTT) levels in Huntington's disease patient-derived fibroblasts (GM04719) by 50% and 25%, respectively, 24 hours after treatment (Figure 3A). A significant decrease in total HTT levels was also observed (Figure 3B). [Figure 4]Figures 4A-4G: Chemical and physical stability of CLP1 in three buffers: Stability of CLP1 in buffer systems at pH 4.5 (Figure 4A), pH 6.5 (Figure 4B), and pH 7.5 (Figure 4C) after 14 days at 40°C. CLP1 did not show fibrillation in any of these buffers using the ThT assay and showed good physical stability at pH 4.5 (Figure 4D), pH 6.5 (Figure 4E), and pH 7.5 (Figure 4F) compared to the positive control (Figure 4G). [Figure 5] Figures 5A-5C: CLP1 is stable in plasma and brain homogenate: CLP1 and CPX showed limited degradation in human plasma (Figure 5A) and mouse plasma (Figure 5B). CLP1 showed higher stability than CPX in mouse brain homogenate (Figure 5C). [Figure 6] Figures 6A-6D: Metabolic stability of CLP1 in liver S9 fraction: Stability of CLP1 in liver S9 fraction from five different species - intrinsic clearance of CLP1 (Figure 6A), intrinsic clearance in 7-ethoxycoumarin-positive control (Figure 6B), CLP1 retention rate (Figure 6C), and retention rate in 7-ethoxycoumarin-positive control (Figure 6D). [Figure 7] Figures 7A and 7B: Free brain fraction of CLP1: Free brain fraction of CLP1 in mouse brain (Figure 7A) and human brain (Figure 7B) measured by LCMS. [Figure 8] Figures 8A-8C: Pharmacokinetics of CLP1 in wild-type mice: Plasma (Figure 8A), whole brain (Figure 8B), and cerebrospinal fluid (Figure 8C) concentrations of CLP1 1-24 hours after injection by LCMS / MS. [Figure 9] Figures 9A-9C: Single injection of CLP1 in wild-type mice: CLP1 showed a strong tendency to increase BDNF after 4 hours (Figure 9A). Post-hoc analysis, using two-way ANOVA, showed a significant time-dependent effect of CLP1 on BDNF levels (p=0.0438) (not shown). CLP1 significantly increased PGC1a 2-4 hours after injection (Figure 9B) and significantly increased transcription factor EB (TFEB) 2-8 hours after injection (Figure 8C). Mean ± SEM. [Figure 10]Figures 10A and 10B: Daily treatment with CLP1 for 7 days in wild-type mice: CLP1 and CPX significantly increased PGC1a at both 0.2 mg / kg and 2 mg / kg daily doses for CLP1 and 13 mg / kg daily dose for CPX (Figure 10A). CLP1 also significantly increased GRN at both 0.2 mg / kg and 2 mg / kg daily doses for CLP1 and 13 mg / kg daily dose for CPX (Figure 10C). CLP1 (0.2 mg / kg) and CPX (13 mg / kg) significantly increased BDNF levels after once-daily subcutaneous administration (Figure 10B). [Figure 11] Figures 11A-11F: CLP1 improves behavior in the R6 / 2 mouse model of Huntington's disease: Schematic diagram of the PoC study in Example 11 (Figure 11A). CLP1 and CPX did not change body weight (Figure 11B). CLP1 significantly improved clasping behavior at weeks 9 and 14 in R6 / 2 treated mice, while CPX improved clasping only at week 9 (Figure 11C). No significant effect was observed with rotarod (Figure 11D). The Kaplan-Meier curve shows cumulative survival (Figure 11E), where CLP1 extended the mean survival by 7 days and the median survival by 13 days in this severe Huntington's disease mouse model of R6 / 2 mice treated (Figure 11F). [Figure 12] Figures 12A-12D: CLP1 improves behavior in a mouse model of Parkinson's disease (MPTP model): Schematic diagram of the experimental design for Example 12 (Figure 12A). Behavioral and biochemical analyses were evaluated on day 10. Treatment with CLP1 significantly increased the distance traveled in the open field test at 2 mg / kg (Figure 12B). CLP1 fully restored grip strength at both 0.2 mg / kg and 2 mg / kg doses (Figure 12C). After MPTP injection, the body weight of the animals initially decreased and gradually increased during the test, but MPTP significantly changed body weight at the endpoint compared to untreated mice (simulations), while CLP1-treated mice did not show a significant change in body weight at the endpoint compared to the simulation group (Figure 12D). [Figure 13]Figures 13A and 13B: CLP1 increases neuronal survival in a mouse model of Parkinson's disease (MPTP model): Tyrosine hydroxylase (TH)+ neurons in the substantia nigra pars compacta (SNpc) of six mice were immunostained and counted as a measure of dopaminergic neuronal survival. The number of positive cells is expressed as the average of three brain sections. Representative images of each group are shown (Figure 13A). TH staining quantification showed a significant effect of CLP1 (0.2 mg / kg) on ​​the survival of TH+ neurons (Figure 13B). [Figure 14] Figures 14A-14F: CLP1 removes human α-synuclein PFF in vivo and reduces its diffusion: A schematic diagram of the experimental design for Example 13 is shown (Figure 14A). The injection site was the amygdala, and both ipsilateral and contralateral diffusion of PFF in the substantia nigra pars compacta and amygdala were evaluated 32 days after treatment (Figure 14B). Representative images of the substantia nigra (Figure 14C) and amygdala (Figure 14D) are shown. CLP1 significantly reduced the number of PFF inclusions in both the ipsilateral substantia nigra (SN) and contralateral amygdala, while also showing a clear tendency to reduce ipsilateral inclusions in the amygdala (Figure 14E). One brain was immunostained for TH+ neurons and imaged (Figure 14F). TH staining indicates the loss of dopaminergic terminals in the dopaminergic striatum in vehicle-treated rats, as the signal was almost completely absent at the injection site. CLP1 treatment significantly preserved dopaminergic terminals. [Figure 15] Figure 15: FSL data: 8-week-old FSL rats were treated once daily for 8 days with 0.2 mg / kg or 2 mg / kg CLP1 or 13 mg / kg CPX in 4.38 mM L-His, 140 mM NaCl, 0.2% Tween-20, and 1500 IU hyaluronidase (pH 6.15). After treatment, hippocampal BDNF levels were assessed by Western blotting normalized to β-actin. The graph shows densitometry quantification of the Western blot bands. BDNF levels were normalized to BDNF levels in control rats (FRL). [Figure 16]Figures 16A-16F: CLP1 increases wakefulness time in Wistar Kyoto rats: Effects of ketamine and CLP1 on wakefulness (Figure 16A), NREM sleep (Figure 16B), and REM sleep (Figure 16C) 0-3 hours post-injection, and wakefulness (Figure 16D), NREM sleep (Figure 16E), and REM sleep (Figure 16F) 11-12 hours post-injection. [Figure 17] Figures 17A-17D: Brain and plasma stability of CLP1-CLP10 and LLP1-LLP10: Stability of peptides CLP1 and LLP1-LLP10 in plasma (Figure 17A) and mouse brain homogenate (Figure 17C), and stability of peptides CLP1-CLP10 in plasma (Figure 17B) and mouse brain homogenate (Figure 17D). [Figure 18] Figures 18A-18D: Effects of CLP1-CLP10 and LLP1-LLP10 on CREB target genes: Effects of CLP1-CLP10 (Figure 18A) and CLP1 and LLP1-LLP10 (Figure 18B) levels on BDNF after 8-24 hours of stimulation with each peptide in primary cortical neurons (Figure 18B), and effects of CLP1-CLP10 (Figure 18C) and CLP1 and LLP1-LLP10 (Figure 18D) levels on PGC1a. [Figure 19] Figures 19A and 19B: CLP1 and CLP10 remove soluble mutant HTT from Huntington's disease patient-derived fibroblasts (GM04719): Peptides CLP1 and CLP10 significantly reduced mutant huntingtin (mHTT) levels in Huntington's disease patient-derived fibroblasts (GM04719) by 50% 24 hours after treatment (measured using a polyglutamine stretch-specific MW1 antibody) (Figure 19A), showing a decrease in total HTT levels (Figure 19B). [Figure 20] Figures 20A-20D: Pharmacokinetics of selected peptides in wild-type mice: Plasma (Figure 20A) and whole brain (Figure 20C) concentrations of cyclic peptides from 1 to 48 hours by LC-MS / MS. Calculated PK levels in plasma (Figure 20B) and brain (Figure 20D). [Figure 21]Figures 21A-21C: In vivo efficacy of selected peptides in wild-type mice: CLP1 significantly increased BDNF levels (Figure 21A), and CLP4 significantly increased tropomyosin receptor kinase B (TrkB) levels (Figure 21C). All mutants significantly increased PGC1a levels (Figure 21B). [Figure 22] Figures 22A-22D: Physical stability of CLP10 in three buffers: Using a ThT assay, CLP10 showed fibrillation in a pH 4.5 buffer (Figure 22A), but was stable in both pH 6.5 (Figure 22B) and pH 7.5 (Figure 22C) buffer systems. The positive control is shown in Figure 22D. [Figure 23] Figures 23A and 23B: Free fractions of CLP1 and CLP10 in the brain: Free fractions of CLP1 and CLP10 in the brain of mouse brain (Figure 23A) and human brain (Figure 23B) measured by LCMS. [Figure 24] Figures 24A and 24B: Pharmacokinetics of CLP10: CLP10 levels are stable in both plasma (Figure 24A) and brain (Figure 24B) 24 hours after injection. [Figure 25] Figure 25: Lipidized peptides LLP11, LLP12, and CLP11 increase BDNF in vivo: BDNF levels in wild-type mice 4–8 hours after injection. [Figure 26] Figure 26: Identification of shorter sequences with activity (CP13-CP17): Activity of CLP1 and non-lipidized cyclic peptides (CP13-CP17 and CPX). [Figure 27] Figures 27A and 27B: Stability of non-lipidized cyclic peptides CP1-CP12: Peptide stability in mouse brain (Figure 27A) and plasma (Figure 27B). [Figure 28] Figures 28A-28C: In vivo efficacy of non-lipidized cyclic peptides CP5-CP12: CP6, CP7, and CP10 significantly increased TFEB (Figure 28A). CP5, CP7, and CP9 significantly increased BDNF (Figure 28B). CP5, CP6, CP7, CP8, and CP10 significantly increased PGC1a levels (Figure 28C). [Figure 29] Figure 29: Effect of amino acid mutations on activity (CP18-CP22): BDNF levels in primary cortical neurons after treatment with non-lipidized cyclic peptides (CP18-CP22 and CPX) compared to CLP1. [Figure 30] Figure 30: Effects of various lipid-modifications on activity (CLP12-CLP15): BDNF levels in primary cortical neurons after treatment with lipid-modified cyclic peptides (CLP12-CLP15) compared to CLP1. [Figure 31] Figures 31A-31C: CLP1 increases GRN and rescues lysosomal dysfunction in a GRN heterozygous mouse model of FTD: Daily subcutaneous administration of CLP1 (0.2 mg / kg) for 7 days in GRN heterozygous mice increases GRN levels (Figure 31A) and normalizes lysosomal proteins LAMP1 (Figure 31B) and p62 (Figure 31C). [Figure 32] Figures 32A-32I: CLP1 rescues behavioral phenotypes in Huntington's disease model zQ175: zQ175 mice showed weight loss compared to wild-type littermates, and the treatment did not affect weight (Figure 32A). Fall latency in rotarod behavioral assessment during the test (Figure 32B). At 12 months of age, fall latency tended to be higher in the treatment groups (CPX and CLP1) compared to zQ175+ vehicles. Number of errors committed during crossing in the transverse beam test (Figure 32C). CLP1 rescued the number of errors committed at 12 months of age, which was also significant compared to the CPX treatment group. Principal component analysis plots (Figure 32D) and hierarchical dendrogram analysis (Figure 32E) of home cage analysis data show behavioral phenotype rescue by CLP1 treatment in zQ175 HD mouse models, but CPX treatment also yielded significant rescue. Individual behavioral parameters of CPX and CLP1 (Figures 32F and 32G, respectively). All zQ175 mice showed higher NfL levels in CSF and blood compared to WT mice (Figures 32H and 32I), and treatment with CLP1 and CPX tended to reduce these levels. [Figure 33]Figures 33A and 33B: CLP1 increases GBA in human iPSC-derived dopaminergic neurons: TFEB and GC-ase levels in hIPSC-derived dopaminergic neurons after CLP1 treatment. [Modes for carrying out the invention]

[0018] (A brief explanation of arrays) [ka] TIFF2026529639000027.tif247170TIFF2026529639000028.tif128170

[0019] (Detailed description of the invention) Provided is a method for the treatment or prevention of disease or disorder of the ear or mastoid process in question, comprising the administration of a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide is (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 That is the method.

[0020] Also provided are peptides or pharmaceutically acceptable salts thereof for use in the treatment or prevention of diseases or disorders of the ear or mastoid process, wherein the peptide is (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 That is the case.

[0021] Further provided is a pharmaceutical composition for the treatment or prevention of diseases or disorders of the ear or mastoid process, comprising a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide is (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 It is a pharmaceutical composition.

[0022] Furthermore, the use of a peptide or a pharmaceutically acceptable salt thereof in the manufacture of a pharmaceutical product for the treatment or prevention of a disease or disorder of the ear or mastoid process, wherein the peptide is (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 That is the case.

[0023] (peptide) In one embodiment, the peptide has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, it may contain a salt thereof, or a lipid-containing cyclic peptide containing a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof.

[0024] Lipidized cyclic peptides have the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or may include a salt thereof. In particular, the peptide is cyclized and all residues of the peptide backbone are connected only by peptide bonds.

[0025] In another embodiment, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, it is a cyclic peptide containing a salt thereof, or a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof (where X2 is P, X3 is anything other than V).

[0026] The cyclic peptide has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or may include a salt thereof, where if X2 is P, X3 is something other than V. In particular, here the peptide is cyclized and all residues of the peptide backbone are connected only by peptide bonds.

[0027] In another embodiment, the peptide comprises 10 or fewer amino acid residues in the ring and has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, it may contain a salt thereof, or a cyclic peptide containing a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof.

[0028] A cyclic peptide may contain 10 or fewer amino acid residues within the ring, and its sequence may be: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or may include a salt thereof. In particular, the peptide is cyclized and all residues of the peptide backbone are connected only by peptide bonds.

[0029] In another embodiment, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, it may contain a salt thereof, or a lipid-containing linear peptide containing a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof.

[0030] Lipidized linear peptides have the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or may include a salt thereof. In particular, here all residues of the peptide backbone are connected only by peptide bonds.

[0031] In another embodiment, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a linear peptide containing a salt thereof, or a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof, where if X2 is P, X3 is something other than V.

[0032] Linear peptides have the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, it may contain a salt thereof, or a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof, where if X2 is P, X3 is something other than V. In particular, here, all residues of the peptide backbone are connected only by peptide bonds.

[0033] In another embodiment, the peptide comprises 10 or fewer amino acid residues in the backbone and has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, it may contain a salt thereof, or a linear peptide containing a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof.

[0034] A linear peptide may contain 10 or fewer amino acid residues in its backbone, and its sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or may include a salt thereof. In particular, here all residues of the peptide backbone are connected only by peptide bonds.

[0035] A "peptide" is a polymer of amino acid residues, usually linked only by peptide bonds.

[0036] In some embodiments, the peptide may be modified. Specific modifications include N-terminal acetylation and / or C-terminal amidation. In some embodiments, the peptide does not contain side-chain modifications. In other embodiments, the peptide is unmodified.

[0037] Certain peptides described herein are cyclic. Peptides can typically be cyclized in four different ways: side chain to side chain, tail to side chain (i.e., C-terminus to side chain), side chain to head (i.e., N-terminus to side chain), and head to tail. As used herein, the term “head-to-tail cyclized peptide” is interchangeable with the term “skeletal cyclized peptide.”

[0038] In one embodiment, the cyclic peptide is a cyclized backbone peptide. In one embodiment, the cyclic peptide is formed by the formation of an amide bond between its N-terminal portion and its C-terminal portion, i.e., cyclization from head to tail. In some embodiments, the peptide is cyclized from side chain to side chain, and the peptide backbone is connected only by peptide bonds. In some embodiments, the peptide is cyclized from tail to side chain, and the peptide backbone is connected only by peptide bonds. In some embodiments, the peptide is cyclized from side chain to head, and the peptide backbone is connected only by peptide bonds.

[0039] In some embodiments, the peptide is cyclized, and the peptide backbone is connected only by peptide bonds.

[0040] In some embodiments, the cyclic peptide includes 25 or fewer amino acid residues in the ring, for example, 20 or fewer amino acid residues in the ring (e.g., including 20 amino acid residues in the ring), in particular 15 or fewer amino acid residues in the ring (e.g., including 15 amino acid residues in the ring), especially 12 or fewer amino acid residues in the ring (e.g., including 12 amino acid residues in the ring), for example 11 or fewer amino acid residues in the ring (e.g., including 11 amino acid residues in the ring).

[0041] In some embodiments, the cyclic peptide contains six or more amino acid residues in the ring, for example, seven or more amino acid residues in the ring (e.g., including seven amino acid residues in the ring), in particular, eight or more amino acid residues in the ring (e.g., including eight amino acid residues in the ring), especially nine or more amino acid residues in the ring (e.g., including nine amino acid residues in the ring), for example, ten or more amino acid residues in the ring (e.g., including ten amino acid residues in the ring). In one embodiment, the cyclic peptide contains eleven or more amino acid residues in the ring (e.g., including eleven amino acid residues in the ring).

[0042] In some embodiments, the linear peptide contains 25 or fewer amino acid residues in the backbone, for example, 20 or fewer amino acid residues in the backbone (for example, 20 amino acid residues in the backbone), in particular 15 or fewer amino acid residues in the backbone (for example, 15 amino acid residues in the backbone), especially 12 or fewer amino acid residues in the backbone (for example, 12 amino acid residues in the backbone), for example 11 or fewer amino acid residues in the backbone (for example, 11 amino acid residues in the backbone).

[0043] In some embodiments, the linear peptide contains six or more amino acid residues in the backbone, for example, seven or more amino acid residues in the backbone (for example, seven amino acid residues in the backbone), in particular eight or more amino acid residues in the backbone (for example, eight amino acid residues in the backbone), especially nine or more amino acid residues in the backbone (for example, nine amino acid residues in the backbone), for example ten or more amino acid residues in the backbone (for example, ten amino acid residues in the backbone). In one embodiment, the linear peptide contains eleven or more amino acid residues in the backbone (for example, eleven amino acid residues in the backbone).

[0044] In some embodiments, all residues within the cyclic peptide are intra-ring.

[0045] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or containing a salt thereof, or containing a conservatively substituted variant of SEQ ID NO: 52 or a salt thereof.

[0046] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, G, X3 represents I, L, A, T, V, X4 represents E, A) or a salt thereof.

[0047] In some embodiments, the peptide has the sequence:

Chemical Formula

[0048] In some embodiments, the peptide has the sequence:

Chemical Formula

[0049] In some embodiments, the peptide has the sequence:

Chemical Formula

[0050] In some embodiments, the peptide has the sequence:

Chemical Formula

[0051] In some embodiments, the peptide has the sequence: Chemical Formula (wherein: X2 represents P, D, Q, K or G, X3 represents I, L, A, T or V, X4 represents E or A) comprises the same or a salt thereof, or comprises a conservatively substituted variant of SEQ ID NO: 55 or a salt thereof.

[0052] In some embodiments, the peptide has the sequence: Chemical Formula (wherein: X2 represents P, D, Q, K or G, X3 represents I, L, A, T or V, X4 represents E or A) or a salt thereof.

[0053] In some embodiments, the peptide has the sequence: Chemical Formula (wherein: X2 represents P, D, Q, K or G, X3 represents I, L, A, T or V, X4 represents E or A) comprises the same or a salt thereof, or comprises a conservatively substituted variant of SEQ ID NO: 56 or a salt thereof.

[0054] In some embodiments, the peptide has the sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or including its salt.

[0055] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or containing a salt thereof, or containing a conservatively substituted variant of SEQ ID NO: 57 or a salt thereof.

[0056] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or including its salt.

[0057] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or containing a salt thereof, or containing a conservatively substituted variant of SEQ ID NO: 58 or a salt thereof.

[0058] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or including its salt.

[0059] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or containing a salt thereof, or containing a conservatively substituted variant of SEQ ID NO: 59 or a salt thereof.

[0060] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or including its salt.

[0061] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or containing a salt thereof, or containing a conservatively substituted variant of SEQ ID NO: 60 or a salt thereof.

[0062] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or including its salt.

[0063] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or containing a salt thereof, or containing a conservatively substituted variant of SEQ ID NO: 61 or a salt thereof.

[0064] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or including its salt.

[0065] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or containing a salt thereof, or containing a conservatively substituted variant of SEQ ID NO: 62 or a salt thereof.

[0066] In some embodiments, the peptide is sequenced as follows: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. or including its salt.

[0067] In some embodiments, X1 represents M. In other embodiments, X1 represents K.

[0068] In some embodiments, X2 represents P. In other embodiments, X2 represents D. In yet another embodiment, X2 represents Q. In an additional embodiment, X2 represents K. In one embodiment, X2 represents G.

[0069] In some embodiments, X3 represents I. In other embodiments, X3 represents L. In further embodiments, X3 represents A. In additional embodiments, X3 represents T. In some embodiments, X3 represents V.

[0070] In some embodiments, X4 represents E. In further embodiments, X4 represents A.

[0071] As will be understood by those skilled in the art, certain amino acid residues can be replaced with other amino acid residues without significantly affecting function (e.g., stability and / or activity). Such substitutions are generally known as conservative substitutions. Typically, conservatively substituted mutants retain at least 50%, e.g., at least 80%, and in particular at least 90% (e.g., at least 100%) of the relevant functional capacity of the unsubstituted reference sequence. For example, functional capacity to increase BDNF, PGC1a, TFEB, and / or phospho-CREB(Ser133) using the assay described herein (e.g., Example 10). Or, functional capacity can be increased using the assay described herein (e.g., Example 9). 1 / 2 AUC, or C max In particular, t in the brain 1 / 2 That's fine.

[0072] The functional capacity is the ability to increase BDNF, PGC1a, TFEB, and / or phospho-CREB(Ser133) using the assay described herein (e.g., Example 10), and the functional capacity is the ability to increase BDNF, PGC1a, TFEB, and / or phospho-CREB(Ser133) using the assay described herein (e.g., Example 9). 1 / 2 , AUC, and / or C max In particular, t in the brain 1 / 2 It is possible.

[0073] A conservatively substituted variant may contain two conservative substitutions. A conservatively substituted variant may contain two conservative substitutions within a specific sequence region (e.g., sequence numbers 51-62). Alternatively, a conservatively substituted variant may contain one conservative substitution. A conservatively substituted variant may contain one conservative substitution within a specific sequence region (e.g., sequence numbers 51-62).

[0074] In some embodiments, the peptide does not contain any conservative substitutions.

[0075] While specific conservative substitutions can be determined empirically, generally preferred substitutions are known, as shown, for example, in Table 1. Table 1 - Common Conservative Substitutions [Table 1]

[0076] Therefore, in some embodiments, the variants include substitution of X1 at position-2. X1 may be replaced by M, e.g., I, (K), L, R, T, V. Alternatively, X1 may be replaced by K, e.g., E, (M), N, Q, R, T. X1 may be replaced by E, N, Q, R, T, I, L, or V.

[0077] In some embodiments, the variant includes substitution of T at position-1, for example, A, K, M, N, R, or S, in particular substitution by A, K, M, N, or R.

[0078] In some embodiments, the variant includes substitution of E at position 0, for example, by A, D, G, K, Q, or V, in particular by substitution by G, K, Q, or V.

[0079] In some embodiments, the variant includes substitution of X2 at position 1. X2 may be a substitute for P, e.g., H, L, (Q), R, or S, in particular H, L, (Q), or R. Alternatively, X2 may be a substitute for D, e.g., A, E, (G), H, N, V, or Y. X2 may be a substitute for Q, e.g., E, H, (K), L, (P), or R. X2 may be a substitute for K, e.g., E, M, N, (Q), R, or T. X2 may be a substitute for G, e.g., A, C, (D), E, ​​or R. X2 may be a substitute for A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y.

[0080] In some embodiments, the variant includes a substitution of X3 at position 2. X3 may be a substitute for I, e.g., F, (L), M, N, or (V). Alternatively, X3 may be a substitute for L, e.g., F, H, (I), M, P, Q, R, (V), or W. X3 may be a substitute for A, e.g., D, E, G, S, or T, in particular D, E, G, or T. X3 may be a substitute for T, e.g., (A), K, M, N, R, or S, in particular (A), K, M, N, or R. X3 may be a substitute for V, e.g., D, E, (I), (L), or M. X3 may be replaced with D, E, F, G, H, K, M, N, P, Q, S, or W, in particular D, E, F, G, H, K, M, N, P, Q, or W.

[0081] In some embodiments, the variant includes substitution of E at position 3, for example, by A, D, G, K, Q, or V, in particular by substitution by G, K, Q, or V.

[0082] In some embodiments, the variants include substitution of H at position 4, for example, substitution by D, L, N, P, Q, R, or Y.

[0083] In some embodiments, the variants include substitution of X4 at position 5. X4 may be replaced by E, (A), D, G, K, Q, or V, etc. Alternatively, X4 may be replaced by D, for example, H, N, or Y. X4 may be replaced by A, for example, D, (E), G, S, or T, in particular D, E, G, or T. X4 may be replaced by G, K, Q, S, T, or V, in particular G, K, Q, T, or V.

[0084] In some embodiments, the variant includes substitution of E at position 6, for example, substitution with A, D, G, K, Q, or V.

[0085] In some embodiments, the variants include substitution of D at position 7, for example, substitution by A, E, G, H, N, V, or Y.

[0086] In some embodiments, the variants include substitution of V at position 8, for example, substitution by D, E, I, L, or M.

[0087] Preferably, the peptide comprises an amino acid sequence selected from any one of SEQ ID NOs: 1-11, 16-42, or 49. Such peptides may also be in the form of salts, for example, pharmaceutically acceptable salts.

[0088] Preferably, the peptide consists of one of CLP1-CLP11, LLP1-LLP12, CP1-CP15, or CP22 (as listed in Tables 2 and 3). Such peptides may be in the form of pharmaceutically acceptable salts. More preferably, the peptide consists of CLP1 or a pharmaceutically acceptable salt thereof. Table 2 - Overview of Lipidized Peptides [Table 2] [ka]

[0089] In CLP1, C18DA-γGlu-OEG-OEG- may be C18DA-L-γGlu-OEG-OEG. Alternatively, in CLP1, C18DA-γGlu-OEG-OEG- may be C18DA-D-γGlu-OEG-OEG. Alternatively, in CLP1, C18DA-γGlu-OEG-OEG- may be a mixture of C18DA-L-γGlu-OEG-OEG and C18DA-D-γGlu-OEG-OEG. Table 3 - Overview of non-lipidized peptides [Table 3] * Listed in WO2022029281

[0090] Preferably, the peptide and its conservatively substituted variants have improved functional capacity compared to CPX, for example, increased BDNF, PGC1a, TFEB, and / or phospho-CREB (Ser133), and / or t 1 / 2 , AUC, or C max (inter alia, all of BDNF, PGC1a, TFEB, phospho-CREB (Ser133), t 1 / 2 , AUC, and C max ). Most preferably, the peptide and its conservatively substituted variants exhibit at least equivalent functional capacity compared to CLP1, for example, functional capacity capable of increasing BDNF, PGC1a, TFEB, and / or phospho-CREB (Ser133), and / or t 1 / 2 , AUC, or C max (inter alia, all of BDNF, PGC1a, TFEB, phospho-CREB (Ser133), t 1 / 2 , AUC, and C max ).

[0091] Preferably, peptides useful in the present invention have one or more of the following properties: - In vitro stability: absence of fibrillation at pH 6.5 and 7.5, preferably at pH 4.5, pH 6.5, and pH 7.5 (e.g., determined by the method of Example 5); - In vivo stability: t of at least 1 hour, preferably at least 4 hours, in particular at least 8 hours 1 / 2 (e.g., determined by the method of Example 9) (e.g., all of the above properties). t 1 / 2 is preferably determined in the brain.

[0092] (Lipidation) As described above, certain peptides useful in the present invention are lipid-modified. Lipidization approaches are outlined in the literature including Ostergaard, 1993; Bech, 2018; van Witteloostuijn, 2016; and Kurtzhals, 2023, which provides further information on lipidization. Ostergaard, 1993; Bech, 2018; van Witteloostuijn, 2016, and Kurtzhals, 2023 are incorporated herein by reference in their entirety to define lipid groups that may be useful in the present invention.

[0093] Many residues, including Cys and Tyr, can be used for lipidation, but lipidation preferably occurs in the side chain of the Lys residue. Lipidation is preferably located towards the N-terminus of the peptide. In the present invention, the lipidated Lys residue is preferably located at X1 (position -2) or X2 (position 1).

[0094] Lipidization may involve the substitution of native amino residues with residues more suitable for lipidization.

[0095] Linking groups are typically used to create a gap between lipid chains and peptides.

[0096] The linker may contain a γGlu residue, particularly L-γGlu. Alternatively, the linker may contain (i) L-Asp, L-Glu, or D-Glu, particularly L-Glu or D-Glu, or (ii) butanoylsulfonamide. The linker may contain multiple residues (e.g., two, three, or four), for example, multiple L-γGlu (e.g., two, three, or four), but conveniently may contain one residue, for example, one γGlu residue (e.g., one L-γGlu).

[0097] The linking group may also contain spacers, such as OEG units, such as 1 to 4 OEG units, or even 2 OEG units. The linking group may contain b-Ala instead of OEG units.

[0098] Common lipid chains include carboxylic acids such as C16, C18, and C20 acids, and dicarboxylic acids such as C18DA and C20DA diacitates. However, other chain lengths and types, such as sulfonic acids or carboxylic acid isosteares like tetrazoles, may also be used depending on the circumstances. Preferably, the lipid chain is C16DA, C18DA, or C20DA, in particular C18DA or C20DA, especially C18DA.

[0099] Preferably, the peptide is lipidized by C18DA-γGlu-OEG-OEG-, for example, C18DA-L-γGlu-OEG-OEG or for example, C18DA-D-γGlu-OEG-OEG.

[0100] Typically, peptides have a single lipid molecule.

[0101] The optimal choice of type and location of lipid deposition can be determined by the structure of the specific peptide.

[0102] (Method for preparing peptides) The useful peptides according to the present invention can be prepared by any method known in the art. Therefore, the peptides can be prepared by standard peptide preparation techniques, such as solution synthesis or Merrifield-type solid-phase synthesis (as illustrated in Examples 1 and 2).

[0103] In one embodiment, the useful peptides according to the present invention are prepared or produced by synthesis. Methods for the synthetic production of peptides are well known in the art. Detailed descriptions and practical advice for producing synthetic peptides can be found in Synthetic Peptides: A User's Guide (Advances in Molecular Biology), edited by Grant GA, Oxford University Press, 2002, or Pharmaceutical Formulation: Development of Peptides and Proteins, edited by Frokjaer and Hovgaard, Literature by Taylor and Francis, 1999. In one embodiment, the useful peptides in the present invention are produced synthetically, particularly by sequence-assisted peptide synthesis (SAPS), solution synthesis, or solid-phase peptide synthesis (SPPS), such as Merrifield solid-phase synthesis.

[0104] For example, after purification of linear peptides by reverse-phase HPLC, the linear peptides can be further processed into cyclic peptides. Techniques for cyclizing peptides and techniques for obtaining cyclic peptides using, for example, a solid support are known (exemplified in Example 2).

[0105] A suitable amino acid sequence, when cyclized, provides the intended cyclic peptide (e.g., CLP1-CLP11, CP1-CP15, or CP22). Side-chain cyclized peptides, head-to-side-chain cyclized peptides, or tail-to-side-chain cyclized peptides require a linear sequence with the usual N-terminus-to-C-terminus residue order. However, a skeletal cyclized peptide consisting of CP1, for example, may be formed from a linear peptide such as MTEPIEHEEDV or VMTEPIEHEED.

[0106] Linear peptides are typically linked only by peptide bonds. Cyclized peptides are typically linked only by peptide bonds. Cyclized peptides may also have a cyclized skeleton.

[0107] The synthetic preparation of linear peptides may require or benefit from the presence of side-chain protecting groups on some or all residues containing reactive side chains, which may be removed, left intact, or removed and reintroduced depending on the specific sequence before the formation of a cyclized peptide, e.g., a skeletal cyclized peptide. If some side-chain protections are present during the formation of a cyclized peptide, e.g., a skeletal cyclized peptide, they may then be removed to form a deprotected cyclized peptide. In the preparation of unskeletal cyclized peptides, protecting groups may be present at the N- or C-terminus as needed.

[0108] Linear peptides and / or cyclized peptides (or, where appropriate, protected versions thereof) may be in the form of salts, in particular pharmaceutically acceptable salts.

[0109] The present invention provides a linear peptide or a protected version thereof, which, when cyclized, provides a cyclic peptide or a protected version thereof as described herein. The present invention provides a linear peptide or a side-chain protected version thereof, which, when cyclized, provides a cyclic peptide or a side-chain protected version thereof as described herein.

[0110] The present invention provides a lipid-modified linear peptide or a protected version thereof, which, when cyclized, provides a lipid-modified cyclic peptide or a protected version thereof as described herein. The present invention provides a lipid-modified linear peptide or a side-chain protected version thereof, which, when cyclized, provides a lipid-modified cyclic peptide or a side-chain protected version thereof as described herein.

[0111] Protected cyclic peptides and protected lipophilized cyclic peptides also form part of the present invention.

[0112] Amino acid protecting groups are known to those skilled in the art and have been discussed, for example, in the literature of Isidro-Llobet et al., Chem Rev 2009 109 2455-2504 and Chandrudu et al., Molecules 2013 18(4):4373-4388. Common side-chain protections include Arg(Pbf), Asn(Trt), Asp(OtBu), Cys(Trt), Gln(Trt), Glu(OtBu), His(Trt), Lys(Boc), Ser(tBu), Thr(tBu), and Tyr(tBu).

[0113] Intermediates useful in the preparation of peptides (i.e., lipid-modified cyclic, cyclic, lipid-modified linear, or linear, and any variant thereof) include such peptides or protected versions thereof covalently bonded to a solid support. Covalent bonding to the solid support may be direct or via spacer groups.

[0114] (medical use) As illustrated in the examples herein, the peptides of the present invention can remove disease-causing aggregates, promote neuronal survival, and improve mitochondrial and lysosome function.

[0115] Preferably, peptides useful in the present invention (lipidized cyclic, cyclic, lipidized linear, or linear, and any variant thereof) or pharmaceutically acceptable salts thereof can increase BDNF levels. More preferably, BDNF levels increase by at least 30% between 0 and 24 hours after administration in the assay of Example 10.

[0116] Preferably, peptides useful in the present invention (lipidized cyclic, cyclic, lipidized linear, or linear, and any variant thereof) or pharmaceutically acceptable salts thereof can increase phospho-CREB(Ser133) levels. More preferably, phospho-CREB(Ser133) levels increase by at least 30% between 0 and 24 hours after administration in the assay of Example 10.

[0117] Preferably, peptides useful in the present invention (lipidized cyclic, cyclic, lipidized linear, or linear, and any variant thereof) or pharmaceutically acceptable salts thereof can increase PGC1a levels. More preferably, PGC1a levels increase by at least 30% between 0 and 24 hours after administration in the assay of Example 10.

[0118] Preferably, peptides useful in the present invention (lipidized cyclic, cyclic, lipidized linear, or linear, and any variant thereof) or pharmaceutically acceptable salts thereof can increase TFEB levels. More preferably, TFEB levels increase by at least 30% between 0 and 24 hours after administration in the assay of Example 10.

[0119] Preferably, peptides useful in the present invention (lipidized cyclic, cyclic, lipidized linear, or linear, and any variant thereof) or pharmaceutically acceptable salts thereof can reduce NfL levels. More preferably, NfL levels are reduced by at least 10%, and in particular at least 20%, in the assay of Example 31.

[0120] In particular, the peptide of the present invention has been shown to mimic the neurotrophic effects induced by the intracellular domain of SorCS2. Loss of SorCS2 has been identified as a causative factor of hearing loss in spontaneously deaf mouse strains, illustrating that SorCS2 may be critical to maintaining cochlear morphology and function. More importantly, the neurotrophic effects of the peptide of the present invention are thought to be transmitted to the IHC-SGN system in hearing loss, thereby restoring synaptic connections, dendritic morphology, and cell number to restore cochlear function after traumatic hearing loss. This is further supported by the evident beneficial effects of the peptide of the present invention on mitochondrial function, a key part of the IHC-SGN pathogenesis in hearing loss (Wong, 2019). This data supports the hypothesis that modulation of the SorCS2 pathway may have therapeutic benefits in patients suffering from ear or mastoid process diseases or disorders.

[0121] Diseases or disorders of the ear or mastoid process are preferably diseases or disorders of the ear or mastoid process that are sensitive to the treatment or prevention according to the present invention. Diseases or disorders of the ear or mastoid process are preferably diseases or disorders of the ear or mastoid process that are sensitive to the modulation of the SorCS2 pathway.

[0122] Diseases or disorders of the ear or mastoid process may be classified as defined in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD), which is incorporated herein by reference to define specific diseases or disorders of the ear or mastoid process.

[0123] In one embodiment, a disease or disorder of the ear or mastoid process is a disease of the inner ear.

[0124] In one embodiment, the inner ear disorder or condition is an acute, episodic, or chronic vestibular syndrome. Vestibular syndromes are characterized by vertigo, dizziness, or unsteadiness. Examples of such vestibular syndromes include vestibular neuritis, otitis cochlea, Meniere's disease, vestibular migraine, benign paroxysmal positional vertigo, superior semicircular canal cleft syndrome, disembarkation syndrome, autoimmune inner ear disorders, vestibular seizures, and persistent postural-induced vertigo. In one embodiment, the inner ear disorder or condition is Meniere's disease. In one embodiment, the inner ear disorder or condition is a vertigo syndrome.

[0125] In one embodiment, a disease or disorder of the ear or mastoid process is a disorder accompanied by hearing loss or hearing impairment.

[0126] In one embodiment, the hearing loss is sensorineural hearing loss, and the cause of the hearing loss lies in the vestibular-cochlear nerve, the inner ear, or the central processing center of the brain.

[0127] In one embodiment, hearing loss is acquired, for example, as a result of noise, disease, trauma, or as a side effect of medicine (ototoxic hearing loss). In an alternative embodiment, hearing loss is congenital hearing loss present at birth.

[0128] In one embodiment, the hearing loss is hereditary. Hereditary hearing loss can be classified as syndromic or non-syndromic. Examples of syndromes associated with syndromic hearing loss include, but are not limited to, Stickler syndrome, Waardenburg syndrome, branchio-otorenal syndrome, CHARGE syndrome, Treacher Collins syndrome, Usher syndrome, Pendred syndrome, Yabel-Lange-Nielsen syndrome, Alport syndrome, and X-linked congenital stape-fixation with perilymphatic spurt. Examples of genes associated with non-syndromic hearing loss include, but are not limited to, GJB2, GJB6, STRC, KCNQ4, TECTA, and POU3F4, as well as mitochondrial DNA (mtDNA) alterations.

[0129] In one embodiment, hereditary hearing loss is a consequence of mitochondrial disorders. Mitochondrial disorders associated with hearing loss include mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), maternal inherited diabetes mellitus and hearing loss (MIDD), Kearns-Sayre syndrome (KSS), and myoclonus epilepsy and red ragged fibers (MERRF).

[0130] In one embodiment, hearing loss is an auditory synaptopathy or neurological disorder in which the subject has normal outer hair cell function, but lacks the synchronous transmission of auditory information due to damage to inner hair cells or their synapses, or damage to spiral ganglion cells or the auditory nerve.

[0131] In one embodiment, the hearing loss is latent hearing loss, where the hearing loss is undetectable by standard hearing tests of hearing thresholds.

[0132] In one embodiment, a disease or disorder of the ear or mastoid process is a cochlear synaptopathy. In some embodiments, cochlear synaptopathy may be associated with aging, sensorineural hearing loss, or noise-induced hearing loss. In some embodiments, cochlear synaptopathy may be associated with inflammatory or neurodegenerative disorders, including Huntington's disease, Parkinson's disease, or Alzheimer's disease.

[0133] In one embodiment, the disease or disorder of the ear or mastoid process is age-related hearing loss.

[0134] The effect of administering the peptide of the present invention on vestibular function can be measured, for example, using balance tests such as the Romberg test and Unterberger test, or video nystagmus testing. Improvements in the number of days affected by rotational vertigo symptoms can also be measured using quality of life surveys.

[0135] The effect of administering the peptide of the present invention on hearing loss can be quantified in various ways. For example, improvement in hearing can be measured using pure-tone audiometry (PTA), auditory brainstem response (ABR; also known as auditory evoked potentials (AEP)), and / or otoacoustic emissions (OAE). Improvement in hearing can also be measured using speech detection threshold (SDT), speech recognition threshold (SRT), word recognition score (WR), auditory input in noise (HINT), American English Matrix Test (AEMT), digit recognition in noise (DIN), word recognition in noise (WIN), speech recognition in noise (SPRINT), or similar tests.

[0136] The effects of administering the peptide of the present invention can be suitably quantified by a speech-in-noise (SIN) test, which can be improved compared to untreated subjects. In particular, the effects of administering the peptide of the present invention can be quantified by a word-in-noise (WIN) test, which can be improved compared to untreated subjects.

[0137] The absolute OAE amplitude may be increased compared to untreated subjects.

[0138] The number of cochlear ribbon synapses, spiral ganglion neuron fibers and / or cells, inner hair cells, and / or outer hair cells may increase, particularly in the high-frequency region of the cochlea.

[0139] In some embodiments, the peptides are for prophylactic use. For example, the peptide therapy for use in the present invention may be administered prior to a series of treatments with ototoxic drugs to prevent or mitigate ototoxicity.

[0140] In other embodiments, the peptide is intended for use in therapies such as the treatment of hearing loss.

[0141] As used herein, the terms “treatment” or “to treat” include controlling, alleviating, reducing, or regulating a disease or disorder or its symptoms.

[0142] The term "prevention" is used herein to mean preventing the symptoms of a disease or disorder in an affected subject or preventing the recurrence of symptoms of a disease or disorder in an affected subject, and is not limited to the complete prevention of the disease.

[0143] Preferably, the subject is a human.

[0144] The human subjects may be, for example, infants under 2 years of age. Alternatively, the subjects may be under 18 years of age, for example, between 2 and 17 years of age. The human subjects may be, for example, adults between 18 and 65 years of age. Alternatively, the human subjects may be 66 years of age or older.

[0145] The subject may be male, or female.

[0146] A “treatment effect” or “therapeutic effect” is defined as a change in the treated state when measured by the criteria that constitute the definitions of the terms “to treat” and “to cure.” A “change” in the treated state is defined as an improvement of at least 5%, preferably 10%, more preferably at least 25%, even more preferably at least 50%, for example at least 75%, and most preferably at least 100% in one of more parameters. This change may be based on an improvement in the severity of the treated state in the individual, or on a difference in the frequency of the improved state between a population of individuals treated with a pharmaceutically acceptable salt of a lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or a pharmaceutically acceptable salt thereof, and a population of individuals that have not received such treatment.

[0147] Preferably, lipid-modified cyclic peptides, cyclic peptides, lipid-modified linear peptides, linear peptides, any variant thereof, and / or pharmaceutically acceptable salts thereof are administered to a subject in need. Preferably, the peptides of the present invention or pharmaceutically acceptable salts thereof are administered in a safe and effective amount, i.e., an amount that yields an acceptable balance between desired benefits and undesirable side effects. A “safe and effective amount” is intended to include an amount that is effective in achieving the desired effect in treatment and / or prevention. The desired effect is usually clinically significant and / or measurable in the context of, for example, (a) preventing the development of a disease, disorder, or disability, particularly when the subject is predisposed or exposed to risk but has not yet been diagnosed; (b) inhibiting a disease, disorder, or disability, i.e., slowing or stopping its onset; and / or (c) mitigating a disease, disorder, or disability, i.e., causing regression of the disease, disorder, or disability or reduction of associated symptoms. A safe and effective amount may be an amount sufficient to achieve the desired effect when the peptide of the present invention or a pharmaceutically acceptable salt thereof is administered alone, or, instead, when administered in combination with one or more further pharmaceutically active ingredients which are either further peptides or pharmaceutically acceptable salts thereof, or different from the peptides of the present invention.

[0148] In one embodiment of the present invention, a lipid-modified cyclic peptide, a cyclic peptide, a lipid-modified linear peptide, a linear peptide, any variant thereof, and / or a pharmaceutically acceptable salt thereof is administered at a dose of 1 μg / day to 200 mg / day.

[0149] In one embodiment of the present invention, a single dose of the peptide is administered, which may contain 1 μg / kg body weight to 100 mg / kg body weight, for example, 1 μg / kg body weight to 10 mg / kg body weight. Preferred doses are about 0.1 mg / kg to about 10 mg / kg, and particularly preferred doses are about 0.1 mg / kg to about 5 mg / kg. The dose according to the present invention may be administered once or several times a day. The administration may also be at intermittent intervals, or at intervals that are not daily. Alternatively, one or more doses may be administered every 2 days, every 3 days, every 4 days, every 5 days, every 6 days, weekly, every 2 weeks, every 3 weeks, every 4 weeks, every 5 weeks, every 6 weeks, or at intervals within these ranges (for example, every 2 to 4 weeks or every 4 to 6 weeks).

[0150] It will be understood that the preferred route of administration will depend on the overall condition and age of the subject to be treated, the nature of the condition to be treated, the location of the tissue in the body to be treated, and the selected peptide of the present invention.

[0151] In one embodiment of the present invention, the administration route allows a lipid-modified cyclic peptide, a cyclic peptide, a lipid-modified linear peptide, a linear peptide, a variant thereof, and / or a pharmaceutically acceptable salt thereof to cross the blood-brain barrier.

[0152] For systemic therapy according to the present invention, the route of administration can involve introducing lipid-modified cyclic peptides, cyclic peptides, lipid-modified linear peptides, linear peptides, any variant thereof, and / or pharmaceutically acceptable salts thereof into the bloodstream to ultimately target the desired site of action. Such a route of administration is any preferred route, e.g., parenteral routes (including subcutaneous, intramuscular, intrathecal, intracerebral, intravenous, and intradermal administration). Parenteral administration is any route of administration other than oral / enteral routes in which the drug avoids first-pass degradation in the liver. Therefore, parenteral administration includes any injection and infusion, e.g., bolus injection or continuous infusion, e.g., intravenous, intramuscular, or subcutaneous administration.

[0153] In one embodiment, administration is, for example, subcutaneous by injection. In one embodiment, administration is, for example, intramuscular by injection. In one embodiment, administration is, for example, intradermal by injection. In one embodiment, administration is, for example, intravenous by injection.

[0154] (Pharmaceutical composition) The lipid-modified cyclic peptides, cyclic peptides, lipid-modified linear peptides, linear peptides, any variants thereof, and / or pharmaceutically acceptable salts thereof of the present invention can be administered as “raw” peptides, but it is preferable to present them in the form of pharmaceutical compositions. Accordingly, the present invention further provides pharmaceutical formulations comprising the lipid-modified cyclic peptides, cyclic peptides, lipid-modified linear peptides, linear peptides, any variants thereof, and / or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable carriers. Pharmaceutical compositions can be prepared by conventional techniques, for example, as described in Remington: The Science and Practice of Pharmacy, 2005, Lippincott, Williams & Wilkins.

[0155] A suitable carrier for pharmaceuticals is water. For better stability, the pharmaceutical composition may be dry and readily reconstituted with water (or, for example, physiological saline).

[0156] A composition that is acceptable as a pharmaceutical for parenteral administration should have a physiologically acceptable pH and a physiologically acceptable osmolality.

[0157] The pH of an aqueous composition can be adjusted considering the components of the composition and the required dosage suitability. The pH is usually at least 4, particularly at least 5, especially at least 5.5, for example, at least 6. The pH is usually 9 or less, particularly 8.5 or less, especially 8 or less, for example, 7.5 or less. The pH may also be between 4 and 9, particularly 5 and 8.5, especially 5.5 and 8, for example, 6.5 and 7.4 (for example, 6.5 and 7.1).

[0158] For parenteral administration, a physiologically acceptable osmolality is desirable to avoid excessive cell deformation or lysis. A physiologically acceptable osmolality usually means that the solution has an osmolality that is nearly isotonic or slightly hypertonic. Preferably, the administration composition has an osmolality of 250-750 mOsm / kg, in particular 250-550 mOsm / kg, especially 270-500 mOsm / kg, for example 270-400 mOsm / kg.

[0159] Other components, such as buffers or stabilizers, may also be present.

[0160] The phrase "medicinally acceptable" is used herein to refer to materials, compositions, dosage forms, etc., that, within the bounds of sound medical judgment, are suitable for use in contact with humans and animals, for example, human tissue, and that do not cause excessive toxicity, irritation, allergic reactions, or other problems or complications, and that are commensurate with a reasonable benefit / risk ratio.

[0161] It will be understood that for use in pharmaceuticals, the salts of peptides should be pharmaceutically acceptable. Suitable pharmaceutically acceptable salts will be obvious to those skilled in the art. Pharmacochemically acceptable salts include those found in Remington's Pharmaceutical Sciences, 17th edition, Mack Publishing Company, Easton, PA, 1985, p. 1418. Such pharmaceutically acceptable salts include acid addition salts formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, or phosphoric acid, and organic acids, such as succinic acid, maleic acid, acetic acid, fumaric acid, citric acid, tartaric acid, benzoic acid, p-toluenesulfonic acid, methanesulfonic acid, or naphthalenesulfonic acid. Pharmacochemically acceptable salts may also be formed with organic bases, such as basic amines, such as ammonia, meglumine, tromethamine, piperazine, arginine, choline, diethylamine, benzathine, or lysine. Salts that are not considered pharmaceutically acceptable may still be useful, for example, in the preparation of peptides and their pharmaceutically acceptable salts.

[0162] Certain peptides can form salts with one equivalent or more of an acid or base. The present invention encompasses all possible stoichiometric and non-stoichiometric forms within its scope.

[0163] If peptides contain basic groups and free acids, they may be zwitterionic.

[0164] The pharmaceutical composition of the present invention can be co-administered with one or more other therapeutic agents. The combined administration of two or more agents can be achieved in several different ways. They may be administered together in a single composition, or they may be administered in separate compositions as part of a combination therapy. For example, one may be administered before or separately from the other, after or sequentially from the other, or simultaneously or in parallel with the other.

[0165] The present invention will be further described with reference to the following clauses:

[0166] (Clause of the present invention) The present invention will be further described with reference to the following clauses: Clause 1. A method for the treatment or prevention of disease or disorder of the ear or mastoid process, comprising the administration of a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide is (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of said peptide (where X2 is P, X3 is something other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a linear peptide containing a conservatively substituted variant of SEQ ID NO: 51. The above method. Clause 2. A peptide or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of diseases or disorders of the ear or mastoid process, wherein the peptide is: (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 The peptide or a pharmaceutically acceptable salt thereof. Article 3. A pharmaceutical composition for the treatment or prevention of diseases or disorders of the ear or mastoid process, comprising a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide is (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 The pharmaceutical composition, which is the aforementioned pharmaceutical composition. Clause 4. The peptide is (i) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide containing or a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A linear peptide containing or a conservatively substituted variant of SEQ ID NO: 51 (where X2 is P, X3 is anything other than V); or (vi) Contains 10 or fewer amino acid residues in the backbone, and sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 The use of peptides or pharmaceutically acceptable salts thereof in the manufacture of pharmaceuticals for the treatment or prevention of diseases or disorders of the ear or mastoid process. Clause A1. The peptide has the sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of a lipid-containing cyclic peptide comprising a salt thereof or a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof, as described in any one of Clauses 1 to 4. Clause A2. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is cyclized. Clause A3. The method described in Clause A2, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the peptide is cyclized and all residues of the peptide skeleton are connected only by peptide bonds. Clause A4. The lipidized cyclic peptide, variant, or salt comprising 25 or fewer amino acid residues in the ring, as described in any one of Clauses A1 to A3, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause A5. The lipidized cyclic peptide, variant, or salt comprising 20 or fewer amino acid residues in the ring, for example, comprising 20 amino acid residues in the ring, the method described in Clause A4, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause A6. The lipidized cyclic peptide, variant, or salt comprising 15 or fewer amino acid residues in the ring, for example, comprising 15 amino acid residues in the ring, the method described in Clause A5, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause A7. The lipidized cyclic peptide, variant, or salt comprising 12 or fewer amino acid residues in the ring, for example, comprising 12 amino acid residues in the ring, the method described in Clause A6, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause A8. The method described in Clause A7, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide, variant, or salt comprises 11 or fewer amino acid residues in the ring. Clause A9. The lipidized cyclic peptide, variant, or salt comprises at least seven amino acid residues in the ring, for example, a method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of any one of Clauses A1 to A8, comprising seven amino acid residues in the ring. Clause A10. The lipidized cyclic peptide, variant, or salt comprising, for example, at least eight amino acid residues in the ring, the method described in Clause A9, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof. Clause A11. The method described in Clause A10, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide, variant, or salt comprises at least nine amino acid residues in the ring, for example, nine amino acid residues in the ring. Clause A12. The lipidized cyclic peptide, variant, or salt comprising, for example, at least 10 amino acid residues in the ring, the method described in Clause A11, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof. Clause A13. The method described in Clause A12, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide, variant, or salt comprises at least 11 amino acid residues in the ring. Clause A14. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide, variant, or salt comprises 11 amino acid residues in the ring. Clause A15. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable method, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable method, a pharmaceutically acceptable method, a pharmaceutically acceptable method, or a pharmaceutically acceptable method, a pharmaceutically acceptable method, or a pharmaceutically acceptable method, a pharmaceutically acceptable method, or a pharmaceutically acceptable method, or a pharmaceutically acceptable method, or a pharmaceutically acceptable method, or a pharmaceutically acceptable method, or a pharmaceutically acceptable method, or a pharmaceutically acceptable method, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method thereof, or a pharmaceutically acceptable method, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable method Clause A16. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses A9 to A14, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 53 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause A17. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 54 or a salt thereof, as described in any one of clauses A10 to A14. Clause A18. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 55 or a salt thereof, as described in any one of clauses A10 to A14. Clause A19. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 56 or a salt thereof, as described in any one of clauses A10 to A14. Clause A20. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 57 or a salt thereof, as described in any one of clauses A11 to A14. Clause A21. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 58 or a salt thereof, as described in any one of clauses A11 to A14. Clause A22. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 59 or a salt thereof, as described in any one of clauses A11 to A14. Clause A23. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 60 or a salt thereof, as described in any one of clauses A12 to A14. Clause A24. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a method according to any one of clauses A12 to A14, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 61 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause A25. The lipidized cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 62 or a salt thereof, as described in any one of clauses A13 to A14. Clause A26. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses A1 to A25, where X1 represents M. Clause A27. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses A1 to A25, wherein X1 represents K. Clause A28. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses A1 to A27, in which X2 represents P. Clause A29. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses A1 to A27, wherein X2 represents D. Clause A30. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses A1 to A27, in which X2 represents Q. Clause A31. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses A1 to A27, wherein X2 represents K. Clause A32. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses A1 to A27, wherein X2 represents G. Clause A33. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses A1 to A32, wherein X3 represents I. Clause A34. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses A1 to A32, in which X3 represents L. Clause A35. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses A1 to A32, wherein X3 represents A. Clause A36. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses A1 to A32, in which X3 represents T. Clause A37. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses A1 to A32, in which X3 represents V. Clause A38. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses A1 to A37, wherein X4 represents E. Clause A39. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses A1 to A37, wherein X4 represents A. Clause A40. The lipidized cyclic peptide, variant, or salt comprises any one sequence of SEQ ID NOs: 1 to 11 or a salt thereof, or a conservatively substituted variant of any one sequence of SEQ ID NOs: 1 to 11 or a salt thereof, for example, consisting of any one sequence of SEQ ID NOs: 1 to 11 or a salt thereof, or consisting of a conservatively substituted variant of any one sequence of SEQ ID NOs: 1 to 11 or a salt thereof, as described in any one of Clauses A13 to A14, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause A41. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use described in any one of Clauses A13 to A14, wherein the lipidized cyclic peptide, variant, or salt comprises the sequence of SEQ ID NO: 1 or a salt thereof, or comprises a conservatively substituted variant of the sequence of SEQ ID NO: 1 or a salt thereof, for example, consisting of the sequence of SEQ ID NO: 1 or a salt thereof, or consisting of a conservatively substituted variant of the sequence of SEQ ID NO: 1 or a salt thereof. Clause A42. The method described in any one of Clauses A1 to A41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the variant or salt thereof comprises two conservative substitutions. Clause A43. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of X1 at position -2, for example, substitution by E, N, Q, R, T, I, L, or V. Clause A44. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause A45. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 0, for example, A, D, G, K, Q, or V, in particular G, K, Q, or V. Clause A46. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use of the variant or salt thereof, comprising substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause A47. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X3 at position 2, for example, by D, E, F, G, H, K, M, N, P, Q, or W, in particular by D, E, F, G, H, K, M, N, P, Q, or W. Clause A48. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 3, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause A49. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause A50. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular G, K, Q, T, or V. Clause A51. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of E at position 6, for example, substitution by A, D, G, K, Q, or V. Clause A52. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of D at position 7, for example, substitution by A, E, G, H, N, V, or Y. Clause A53. The method described in any one of Clauses A1 to A42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of V at position 8, for example, substitution by D, E, I, L, or M. Clause A54. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of X1 at position -2, for example, substitution by E, N, Q, R, T, I, L, or V. Clause A55. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of T at position-1, for example, substitution A, K, M, N, R, or S, in particular A, K, M, N, or R. Clause A56. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 0, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause A57. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause A58. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X3 at position 2, for example, by D, E, F, G, H, K, M, N, P, Q, or W, in particular by D, E, F, G, H, K, M, N, P, Q, or W. Clause A59. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of E at position 3, for example, substitution by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause A60. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause A61. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular G, K, Q, T, or V. Clause A62. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of E at position 6, for example, substitution by A, D, G, K, Q, or V. Clause A63. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of D at position 7, for example, substitution by A, E, G, H, N, V, or Y. Clause A64. The method described in any one of Clauses A42 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of V at position 8, for example, substitution by D, E, I, L, or M. Clause A65. The method described in any one of Clauses A43 to A53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises one conservative substitution. Clause A66. The method described in any one of Clauses A1 to A41, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use wherein the peptide is a lipid-modified cyclic peptide or a salt thereof. Clause A67. The method described in any one of Clauses A1 to A66, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use comprising the lipidized cyclic peptide, variant, or salt of which the K residue is lipidized. Clause A68. The method described in Clause A67, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized K residue is X2 at position 1. Clause A69. The method according to Clause A67, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized K residue is X1 at position-2. Clause A70. The method, peptide for use or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use according to any one of Clauses A1 to A69, wherein the lipid chain is a C16DA, C18DA, or C20DA group. Clause A71. The method described in Clause A70, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipid chain is a C18DA group. Clause A72. The method according to any one of Clauses A1 to A71, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the lipid is linked to the K residue via γGlu. Clause A73. The method described in Clause A72, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipid is linked to the K residue via γGlu and 1 to 4 OEG groups. Clause A74. The method described in Clause A73, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipid is linked to the K residue via γGlu and two OEG groups. Clause A75. The method described in any one of Clauses A1 to A69, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use wherein the lipid is C18DA-γGlu-OEG-OEG-. Clause A76. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, according to any one of Clauses A1 to A69, wherein the lipid is C18DA-γGlu-OEG-OEG-. Clause A77. The method described in Clause A75 or A76, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipid is C18DA-L-γGlu-OEG-OEG-. Clause A78. The method described in Clause A75 or A76, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipid is C18DA-D-γGlu-OEG-OEG-. Clause A79. The method described in Clause A1, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use comprising CLP1 or a salt thereof. Clause A80. A peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use comprising CLP1, wherein the lipid is C18DA-L-γGlu-OEG-OEG- or a salt thereof, as described in Clause A1. Clause A81. A peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use comprising CLP1, wherein the lipid is C18DA-D-γGlu-OEG-OEG- or a salt thereof, as described in Clause A1. Clause A82. The method described in Clause A1, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use comprising CLP2 or a salt thereof. Clause A83. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide or salt thereof comprises CLP3 or a salt thereof. Clause A84. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide or salt thereof comprises CLP4 or a salt thereof. Clause A85. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide or salt thereof comprises CLP5 or a salt thereof. Clause A86. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide or salt thereof comprises CLP6 or a salt thereof. Clause A87. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide or salt thereof comprises CLP7 or a salt thereof. Clause A88. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide or salt thereof comprises CLP8 or a salt thereof. Clause A89. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide or salt thereof comprises CLP9 or a salt thereof. Clause A90. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide or salt thereof comprises CLP10 or a salt thereof. Clause A91. The method described in Clause A1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized cyclic peptide or a salt thereof comprises CLP11 or a salt thereof. Clause A92. The method described in any one of Clauses A1 to A91, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the salt is a pharmaceutically acceptable salt. Clause A93. Any method described in the preceding Clause A, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a lipid-modified cyclic peptide. Clause A94. Any method described in the preceding Clause A, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a lipid-modified mutant peptide. Clause A95. Any method described in the preceding Clause A, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of a lipid-modified cyclic peptide. Clause A96. Any method described in the preceding Clause A, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of a lipid-modified mutant peptide. Clause A97. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipidized cyclic peptide, in which the side chain is not modified, as described in any one of Clauses A1 to A96. Clause A98. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipid-modified cyclic peptide as described in any one of Clauses A1 to A96, in which the lipid-modified cyclic peptide is not modified. Clause B1. The peptide has the sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of a cyclic peptide containing a salt thereof, or a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof (wherein X2 is P, X3 is something other than V), as described in any one of Clauses 1 to 4. Clause B2. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is cyclized. Clause B3. The method described in Clause B2, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the peptide is cyclized and all residues of the peptide skeleton are connected only by peptide bonds. Clause B4. The cyclic peptide, variant, or salt comprising 25 or fewer amino acid residues in the ring, as described in any one of Clauses B1 to B3, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B5. The cyclic peptide, variant, or salt comprising 20 or fewer amino acid residues in the ring, for example, comprising 20 amino acid residues in the ring, the method described in Clause B4, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B6. The cyclic peptide, variant, or salt comprising 15 or fewer amino acid residues in the ring, for example, comprising 15 amino acid residues in the ring, the method described in Clause B5, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B7. The cyclic peptide, variant, or salt comprising 12 or fewer amino acid residues in the ring, for example, comprising 12 amino acid residues in the ring, the method described in Clause B6, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B8. The method described in Clause B7, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide, variant, or salt comprises 11 or fewer amino acid residues in the ring. Clause B9. The cyclic peptide, variant, or salt comprises at least seven amino acid residues in the ring, for example, a method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use of any one of Clauses B1 to B8, comprising seven amino acid residues in the ring. Clause B10. The cyclic peptide, variant, or salt comprising, for example, at least eight amino acid residues in the ring, the method described in Clause B9, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof. Clause B11. The cyclic peptide, variant, or salt comprising, for example, at least nine amino acid residues within the ring, the method described in Clause B10, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof. Clause B12. The cyclic peptide, variant, or salt comprising, for example, at least 10 amino acid residues in the ring, the method described in Clause B11, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof. Clause B13. The method described in Clause B12, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide, variant, or salt comprises at least 11 amino acid residues in the ring. Clause B14. The cyclic peptide, variant, or salt comprising 11 amino acid residues in the ring, as described in Clause B1, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B15. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses B9 to B14, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 52 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B16. Cyclic peptides, variants, or salts may have the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a method according to any one of clauses B9 to B14, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 53 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B17. Cyclic peptides, variants, or salts may have the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses B10 to B14, comprising a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 54 or a salt thereof. Clause B18. Cyclic peptides, variants, or salts may have the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses B10 to B14, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 55 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B19. Cyclic peptides, variants, or salts may have the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses B10 to B14, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 56 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B20. Cyclic peptides, variants, or salts may have the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 57 or a salt thereof, as described in any one of the clauses B11 to B14. Clause B21. Cyclic peptides, variants, or salts may have the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses B11 to B14, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 58 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B22. Cyclic peptides, variants, or salts may have the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 59 or a salt thereof, as described in any one of the clauses B11 to B14. Clause B23. Cyclic peptides, variants, or salts may have the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a method according to any one of clauses B12 to B14, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 60 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B24. Cyclic peptides, variants, or salts may have the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a method according to any one of clauses B12 to B14, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 61 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B25. Cyclic peptides, variants, or salts may have the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a method according to any one of clauses B13 to B14, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 62 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B26. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1 to B25, wherein X1 represents M. Clause B27. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1 to B25, wherein X1 represents K. Clause B28. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1 to B27, wherein X2 represents P. Clause B29. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1 to B27, wherein X2 represents D. Clause B30. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1 to B27, wherein X2 represents Q. Clause B31. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1 to B27, wherein X2 represents K. Clause B32. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1 to B27, wherein X2 represents G. Clause B33. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1 to B32, wherein X3 represents I. Clause B34. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1 to B32, wherein X3 represents L. Clause B35. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses B1 to B32, wherein X3 represents A. Clause B36. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1 to B32, in which X3 represents T. Clause B37. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses B1-B27 or B29-B32, in which X3 represents V. Clause B38. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses B1 to B37, wherein X4 represents E. Clause B39. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses B1 to B37, wherein X4 represents A. Clause B40. The cyclic peptide, variant, or salt comprises any one sequence of SEQ ID NOs: 1-10 and 28-39 or a salt thereof, or a conservatively substituted variant of any one sequence of SEQ ID NOs: 1-10 and 28-39 or a salt thereof, for example, consisting of any one sequence of SEQ ID NOs: 1-10 and 28-39 or a salt thereof, or consisting of any one conservatively substituted variant of any one sequence of SEQ ID NOs: 1-10 and 28-39 or a salt thereof, as described in any one of Clauses B13-B14, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B41. The cyclic peptide, variant, or salt comprises the sequence of SEQ ID NO: 1 or a salt thereof, or comprises a conservatively substituted variant of SEQ ID NO: 1 or a salt thereof, for example, consisting of the sequence of SEQ ID NO: 1 or a salt thereof, or consisting of a conservatively substituted variant of SEQ ID NO: 1 or a salt thereof, as described in any one of Clauses B13 to B14, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B42. The method described in any one of Clauses B1 to B41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the variant or salt thereof comprises two conservative substitutions. Clause B43. The method described in any one of Clauses B1 to B42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X1 at position -2, for example, a substitution by E, N, Q, R, T, I, L, or V. Clause B44. The method described in any one of Clauses B1 to B42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause B45. The method described in any one of Clauses B1 to B42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 0, for example, by A, D, G, K, Q, or V, in particular by substitution by G, K, Q, or V. Clause B46. The method described in any one of Clauses B1 to B42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause B47. The method described in any one of Clauses B1 to B42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X3 at position 2, for example, by D, E, F, G, H, K, M, N, P, Q, or W, in particular by D, E, F, G, H, K, M, N, P, Q, or W. Clause B48. The method described in any one of Clauses B1 to B42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 3, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause B49. The method described in any one of Clauses B1 to B42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause B50. The method described in any one of Clauses B1 to B42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular G, K, Q, T, or V. Clause B51. The method described in any one of Clauses B1 to B42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of E at position 6, for example, substitution by A, D, G, K, Q, or V. Clause B52. The method described in any one of Clauses B1 to B42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of D at position 7, for example, by A, E, G, H, N, V, or Y. Clause B53. The method described in any one of Clauses B1 to B42, wherein the variant or salt thereof comprises a substitution of V at position 8, for example, by D, E, I, L, or M, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B54. The method described in any one of Clauses B42 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X1 at position -2, for example, a substitution by E, N, Q, R, T, I, L, or V. Clause B55. The method described in any one of Clauses B42 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause B56. The method described in any one of Clauses B42 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 0, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause B57. The method described in any one of Clauses B42 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause B58. The method described in any one of Clauses B42 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X3 at position 2, for example, by D, E, F, G, H, K, M, N, P, Q, or W, in particular by D, E, F, G, H, K, M, N, P, Q, or W. Clause B59. The method described in any one of Clauses B42 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 3, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause B60. The method described in any one of Clauses B42 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause B61. The method described in any one of Clauses B42 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X4 at position 5, for example, by G, K, Q, S, T, or V, in particular by substitution by G, K, Q, T, or V. Clause B62. The method described in any one of Clauses B42 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of E at position 6, for example, substitution by A, D, G, K, Q, or V. Clause B63. The method described in any one of Clauses B42 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of D at position 7, for example, a substitution by A, E, G, H, N, V, or Y. Clause B64. The method described in any one of Clauses B42 to B53, wherein the variant or salt thereof comprises a substitution of V at position 8, for example, by D, E, I, L, or M, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause B65. The method described in any one of Clauses B43 to B53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises one conservative substitution. Clause B66. The method described in any one of Clauses B1 to B41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a cyclic peptide or a salt thereof. Clause B67. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the cyclic peptide or salt comprises SEQ ID NO: 1 or a salt thereof. Clause B68. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises SEQ ID NO: 2 or a salt thereof. Clause B69. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises SEQ ID NO: 3 or a salt thereof. Clause B70. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises SEQ ID NO: 4 or a salt thereof. Clause B71. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises Sequence ID No. 5 or a salt thereof. Clause B72. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises SEQ ID NO: 6 or a salt thereof. Clause B73. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises Sequence ID No. 7 or a salt thereof. Clause B74. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises Sequence ID No. 8 or a salt thereof. Clause B75. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises SEQ ID NO: 9 or a salt thereof. Clause B76. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises SEQ ID NO: 10 or a salt thereof. Clause B77. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP1 or a salt thereof. Clause B78. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP2 or a salt thereof. Clause B79. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP3 or a salt thereof. Clause B80. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP4 or a salt thereof. Clause B81. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP5 or a salt thereof. Clause B82. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP6 or a salt thereof. Clause B83. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP7 or a salt thereof. Clause B84. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP8 or a salt thereof. Clause B85. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP9 or a salt thereof. Clause B86. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP10 or a salt thereof. Clause B87. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP11 or a salt thereof. Clause B88. The method described in Clause B1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP12 or a salt thereof. Clause B89. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use described in any one of Clauses B1 to B98, wherein the salt is a pharmaceutically acceptable salt. Clause B90. Any method described in the preceding Clause B, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a cyclic peptide. Clause B91. Any method described in the preceding Clause B, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a mutant peptide. Clause B92. Any method described in the preceding Clause B, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of a cyclic peptide. Clause B93. Any method described in the preceding Clause B, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of the mutant peptide. Clause B94. The method described in any one of Clauses B1 to B93, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the cyclic peptide is not side-chain modified. Clause B95. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the cyclic peptide in which the cyclic peptide is not modified, as described in any one of Clauses B1 to B93. Clause C1. The peptide contains 10 or fewer amino acid residues in the ring, and its sequence is: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of a cyclic peptide comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof, as described in any one of Clauses 1 to 28. Clause C2. The method described in Clause C1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is cyclized. Clause C3. The method described in Clause C2, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the peptide is cyclized and all residues of the peptide skeleton are connected only by peptide bonds. Clause C4. The cyclic peptide, variant, or salt comprising six amino acid residues within the ring, as described in any one of Clauses C1 to C3, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C5. The cyclic peptide, variant, or salt comprising seven amino acid residues in the ring, as described in any one of Clauses C1 to C3, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C6. The cyclic peptide, variant, or salt comprising eight amino acid residues in the ring, as described in any one of Clauses C1 to C3, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C7. The cyclic peptide, variant, or salt comprising nine amino acid residues in the ring, as described in any one of Clauses C1 to C3, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C8. The cyclic peptide, variant, or salt comprising 10 amino acid residues in the ring, as described in any one of Clauses C1 to C3, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C9. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses C1-C3 or C5-C8, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 52 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C10. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses C1-C3 or C5-C8, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 53 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C11. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses C1-C3 or C6-C8, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 54 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C12. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A cyclic peptide, variant, or salt according to any one of the clauses C1-C3 or C6-C8, or comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 55 or a salt thereof. Clause C13. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses C1-C3 or C6-C8, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 56 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C14. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses C1-C3 or C7-C8, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 57 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C15. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a method according to any one of clauses C1-C3 or C7-C8, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 58 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C16. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses C1-C3 or C7-C8, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 59 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C17. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses C1-C3 or C8, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 60 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C18. The cyclic peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses C1-C3 or C8, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 61 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C19. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C18, where X1 represents M. Clause C20. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C18, where X1 represents K. Clause C21. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C20, where X2 represents P. Clause C22. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C20, wherein X2 represents D. Clause C23. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C20, where X2 represents Q. Clause C24. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C20, wherein X2 represents K. Clause C25. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C20, wherein X2 represents G. Clause C26. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C25, wherein X3 represents I. Clause C27. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C25, where X3 represents L. Clause C28. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C25, in which X3 represents A. Clause C29. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C25, wherein X3 represents T. Clause C30. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C25, in which X3 represents V. Clause C31. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C30, where X4 represents E. Clause C32. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses C1 to C30, wherein X4 represents A. Clause C33. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use according to any one of Clauses C1 to C32, wherein the cyclic peptide sequence is (i) a part of or a salt thereof of any one of SEQ ID NOs: 1-10 and 28-39, or (ii) a conservatively substituted variant or a salt thereof of any one of SEQ ID NOs: 1-10 and 28-39. Clause C34. The method according to Clause C33, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide sequence is (i) a part of SEQ ID NO: 1 or a salt thereof, or (ii) a conservatively substituted variant of SEQ ID NO: 1 or a salt thereof. Clause C35. The cyclic peptide, variant, or salt comprises any one sequence of SEQ ID NOs. 40-42 or a salt thereof, or a conservatively substituted variant of any one sequence of SEQ ID NOs. 40-42 or a salt thereof, for example, consisting of any one sequence of SEQ ID NOs. 40-42 or a salt thereof, or consisting of any one conservatively substituted variant of any one sequence of SEQ ID NOs. 40-42 or a salt thereof, as described in any one of Clauses C1-C32, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C36. The method according to any one of Clauses C1 to C35, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises two conservative substitutions. Clause C37. The method described in any one of Clauses C1 to C36, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X1 at position -2, for example, a substitution by E, N, Q, R, T, I, L, or V. Clause C38. The method described in any one of Clauses C1 to C36, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause C39. The method described in any one of Clauses C1 to C36, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of E at position 0, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause C40. The method according to any one of Clauses C1 to C36, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause C41. The method described in any one of Clauses C1 to C36, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X3 at position 2, for example, D, E, F, G, H, K, M, N, P, Q, or W, in particular D, E, F, G, H, K, M, N, P, Q, or W. Clause C42. The method described in any one of Clauses C1 to C36, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 3, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause C43. The method described in any one of Clauses C1 to C36, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause C44. The method described in any one of Clauses C1 to C36, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular substitution by G, K, Q, T, or V. Clause C45. The method described in any one of Clauses C1 to C36, wherein the variant or salt thereof comprises a substitution of E at position 6, for example, by A, D, G, K, Q, or V, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C46. The method described in any one of Clauses C1 to C36, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of D at position 7, for example, substitution by A, E, G, H, N, V, or Y. Clause C47. The method described in any one of Clauses C1 to C36, wherein the variant or salt thereof comprises a substitution of V at position 8, for example, by D, E, I, L, or M, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C48. The method described in any one of Clauses C36 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X1 at position -2, for example, a substitution by E, N, Q, R, T, I, L, or V. Clause C49. The method described in any one of Clauses C36 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause C50. The method described in any one of Clauses C36 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of E at position 0, for example, A, D, G, K, Q, or V, in particular G, K, Q, or V. Clause C51. The method described in any one of Clauses C36 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause C52. The method described in any one of Clauses C36 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X3 at position 2, for example, D, E, F, G, H, K, M, N, P, Q, or W, in particular D, E, F, G, H, K, M, N, P, Q, or W. Clause C53. The method described in any one of Clauses C36 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of E at position 3, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause C54. The method described in any one of Clauses C36 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause C55. The method described in any one of Clauses C36 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular G, K, Q, T, or V. Clause C56. The method described in any one of Clauses C36 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of E at position 6, for example, by A, D, G, K, Q, or V. Clause C57. The method described in any one of Clauses C36 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of D at position 7, for example, by A, E, G, H, N, V, or Y. Clause C58. The method described in any one of Clauses C36 to C47, wherein the variant or salt thereof comprises a substitution of V at position 8, for example, by D, E, I, L, or M, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause C59. The method according to any one of Clauses C37 to C47, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises one conservative substitution. Clause C60. The method according to any one of Clauses C1 to C35, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a cyclic peptide or a salt thereof. Clause C61. The method according to Clause C1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the cyclic peptide or salt comprises CP13 or a salt thereof. Clause C62. The method according to Clause C1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the cyclic peptide or salt comprises CP14 or a salt thereof. Clause C63. The method described in Clause C1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide or salt comprises CP15 or a salt thereof. Clause C64. A method according to any one of Clauses C1 to C63, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the salt is a pharmaceutically acceptable salt. Clause C65. Any method described in the preceding Clause C, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a cyclic peptide. Clause C66. Any method described in the preceding Clause C, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a mutant peptide. Clause C67. Any method described in the preceding Clause C, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of a cyclic peptide. Clause C68. Any method described in the preceding Clause C, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of the mutant peptide. Clause C69. The method according to any one of Clauses C1 to C68, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the cyclic peptide is not side-chain modified. Clause C70. The method described in any one of Clauses C1 to C68, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the cyclic peptide which is not modified. Clause D1. The peptide has the sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of a lipid-containing linear peptide comprising a salt thereof or a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof, as described in any one of Clauses 1 to 4. Clause D2. The method described in Clause D1, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein all residues of the peptide skeleton are connected only by peptide bonds. Clause D3. The method according to Clause D1 or D2, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide, variant, or salt comprises 25 or fewer amino acid residues in the backbone. Clause D4. The method described in Clause D3, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the lipidized linear peptide, variant, or salt comprises 20 or fewer amino acid residues in the backbone, for example, 20 amino acid residues in the backbone. Clause D5. The method described in Clause D4, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the lipidized linear peptide, variant, or salt comprises 15 or fewer amino acid residues in the backbone, for example, 15 amino acid residues in the backbone. Clause D6. The method described in Clause D5, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the lipidized linear peptide, variant, or salt comprises 12 or fewer amino acid residues in the backbone, for example, 12 amino acid residues in the backbone. Clause D7. The method described in Clause D6, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide, variant, or salt comprises 11 or fewer amino acid residues in the backbone. Clause D8. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipidized linear peptide, variant, or salt comprising, for example, seven amino acid residues in the skeleton, comprising, for example, seven amino acid residues in the skeleton, according to any one of Clauses D1 to D7. Clause D9. The method described in Clause D8, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide, variant, or salt comprises at least eight amino acid residues in the backbone, for example, the eight amino acid residues in the backbone. Clause D10. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipidized linear peptide, variant, or salt comprising, for example, at least nine amino acid residues in the backbone, comprising the nine amino acid residues in the backbone, as described in Clause D9. Clause D11. The method according to Clause D10, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide, variant, or salt comprises at least 10 amino acid residues in the backbone, for example, the 10 amino acid residues in the backbone. Clause D12. The method according to Clause D11, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide, variant, or salt comprises at least 11 amino acid residues in the backbone. Clause D13. The method according to Clause D12, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide, variant, or salt comprises 11 amino acid residues in the backbone. Clause D14. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, according to any one of the clauses D8 to D13, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 52 or a salt thereof. Clause D15. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses D8 to D13, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 53 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause D16. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, according to any one of the clauses D9 to D13, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 54 or a salt thereof. Clause D17. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, according to any one of the clauses D9 to D13, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 55 or a salt thereof. Clause D18. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, according to any one of the clauses D9 to D13, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 56 or a salt thereof. Clause D19. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses D10 to D13, comprising a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 57 or a salt thereof. Clause D20. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses D10 to D13, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 58 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause D21. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a method according to any one of the clauses D10 to D13, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 59 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause D22. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses D11 to D23, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 60 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause D23. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses D11 to D13, comprising a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 61 or a salt thereof. Clause D24. The lipidized linear peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses D12 to D13, comprising a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 62 or a salt thereof. Clause D25. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses D1 to D24, wherein X1 represents M. Clause D26. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses D1 to D24, wherein X1 represents K. Clause D27. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses D1 to D26, wherein X2 represents P. Clause D28. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses D1 to D26, wherein X2 represents D. Clause D29. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses D1 to D26, wherein X2 represents Q. Clause D30. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses D1 to D26, wherein X2 represents K. Clause D31. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses D1 to D26, wherein X2 represents G. Clause D32. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses D1 to D31, wherein X3 represents I. Clause D33. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses D1 to D31, in which X3 represents L. Clause D34. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses D1 to D31, wherein X3 represents A. Clause D35. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses D1 to D31, in which X3 represents T. Clause D36. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses D1 to D31, in which X3 represents V. Clause D37. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses D1 to D36, wherein X4 represents E. Clause D38. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses D1 to D36, wherein X4 represents A. Clause D39. The lipidized linear peptide, variant, or salt comprises any one sequence of SEQ ID NOs: 1 to 11 or a salt thereof, or a conservatively substituted variant of any one sequence of SEQ ID NOs: 1 to 11 or a salt thereof, for example, consisting of any one sequence of SEQ ID NOs: 1 to 11 or a salt thereof, or consisting of any one conservatively substituted variant of any one sequence of SEQ ID NOs: 1 to 11 or a salt thereof, as described in any one of Clauses D13 to D14, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause D40. The lipidized linear peptide, variant, or salt comprises the sequence of SEQ ID NO: 1 or a salt thereof, or comprises a conservatively substituted variant of SEQ ID NO: 1 or a salt thereof, for example, consisting of the sequence of SEQ ID NO: 1 or a salt thereof, or consisting of a conservatively substituted variant of SEQ ID NO: 1 or a salt thereof, as described in any one of Clauses D13 to D14, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause D41. The lipidized linear peptide, variant, or salt comprises any one sequence of LLP1 to LLP12 or a salt thereof, or a conservatively substituted variant of any one sequence of LLP1 to LLP12 or a salt thereof, for example, consisting of any one sequence of LLP1 to LLP12 or a salt thereof, or consisting of any one conservatively substituted variant of any one sequence of LLP1 to LLP12 or a salt thereof, as described in any one of Clauses D13 to D14, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause D42. The method according to any one of Clauses D1 to D41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises two conservative substitutions. Clause D43. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X1 at position -2, for example, a substitution by E, N, Q, R, T, I, L, or V. Clause D44. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause D45. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 0, for example, A, D, G, K, Q, or V, in particular G, K, Q, or V. Clause D46. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use of the variant or salt thereof, comprising substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause D47. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X3 at position 2, for example, by D, E, F, G, H, K, M, N, P, Q, or W, in particular by D, E, F, G, H, K, M, N, P, Q, or W. Clause D48. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of E at position 3, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause D49. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause D50. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular G, K, Q, T, or V. Clause D51. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of E at position 6, for example, by A, D, G, K, Q, or V. Clause D52. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of D at position 7, for example, a substitution by A, E, G, H, N, V, or Y. Clause D53. The method described in any one of Clauses D1 to D42, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of V at position 8, for example, substitution by D, E, I, L, or M. Clause D54. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X1 at position -2, for example, a substitution by E, N, Q, R, T, I, L, or V. Clause D55. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause D56. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 0, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause D57. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause D58. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X3 at position 2, for example, D, E, F, G, H, K, M, N, P, Q, or W, in particular D, E, F, G, H, K, M, N, P, Q, or W. Clause D59. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of E at position 3, for example, substitution by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause D60. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause D61. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular G, K, Q, T, or V. Clause D62. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of E at position 6, for example, by A, D, G, K, Q, or V. Clause D63. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of D at position 7, for example, substitution by A, E, G, H, N, V, or Y. Clause D64. The method described in any one of Clauses D42 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of V at position 8, for example, substitution by D, E, I, L, or M. Clause D65. The method described in any one of Clauses D43 to D53, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises one conservative substitution. Clause D66. The method described in any one of Clauses D1 to D41, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use wherein the peptide is a lipidized linear peptide or a salt thereof. Clause D67. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipidized linear peptide, variant, or salt comprising a lipidized K residue, as described in any one of Clauses D1 to D66. Clause D68. The method according to Clause D67, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized K residue is X2 at position 1. Clause D69. The method according to Clause D67, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized K residue is X1 at position-2. Clause D70. The method, peptide for use or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use according to any one of Clauses D1 to D69, wherein the lipid chain is a C16DA, C18DA, or C20DA group. Clause D71. The method described in Clause D70, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipid chain is a C18DA group. Clause D72. The method according to any one of Clauses D1 to D71, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the lipid is linked to the K residue via γGlu. Clause D73. The method according to Clause D72, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipid is linked to the K residue via γGlu and 1 to 4 OEG groups. Clause D74. The method according to Clause D73, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipid is linked to the K residue via γGlu and two OEG groups. Clause D75. The method described in any one of Clauses D1 to D69, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use thereof, wherein the lipid is C18DA-γGlu-OEG-OEG-. Clause D76. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use according to any one of Clauses D1 to D69, wherein the lipid is C18DA-γGlu-OEG-OEG-. Clause D77. The method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use according to either Clause D75 or D76, wherein the lipid is C18DA-L-γGlu-OEG-OEG-. Clause D78. The method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use according to either Clause D75 or D76, wherein the lipid is C18DA-D-γGlu-OEG-OEG-. Clause D79 The method according to any one of Clauses D1 to D78, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the lipidized linear peptide, variant, or salt is acetylated at the N-terminus. Clause D80. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipidized linear peptide, variant, or salt, which is not modified at the N-terminus, as described in any one of Clauses D1 to D78. Clause D81. The method described in any one of Clauses D1 to D80, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide, variant, or salt is amidated at the C-terminus. Clause D82. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipidized linear peptide, variant, or salt, which is not modified at the C-terminus, as described in any one of Clauses D1 to D80. Clause D83. The method according to Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the lipidized linear peptide or salt comprises LLP1 or a salt thereof. Clause D84. The lipidized linear peptide or salt according to Clause D1, wherein the lipidized linear peptide or salt comprises LLP2 or a salt thereof. Clause D85. The method described in Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide or salt comprises LLP3 or a salt thereof. Clause D86. The method described in Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide or salt comprises LLP4 or a salt thereof. Clause D87. The method described in Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide or salt comprises LLP5 or a salt thereof. Clause D88. The method according to Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide or salt comprises LLP6 or a salt thereof. Clause D89. The method described in Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide or salt comprises LLP7 or a salt thereof. Clause D90. The method according to Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide or salt comprises LLP8 or a salt thereof. Clause D91. The method according to Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide or salt comprises LLP9 or a salt thereof. Clause D92. The method according to Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide or salt comprises LLP10 or a salt thereof. Clause D93. The method described in Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide or salt comprises LLP11 or a salt thereof. Clause D94. The method described in Clause D1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide or salt comprises LLP12 or a salt thereof. Clause D95. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, according to any one of Clauses D1 to D95, wherein the salt is a pharmaceutically acceptable salt. Clause D96. Any method described in the preceding Clause D, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a lipidized linear peptide. Clause D97. Any method described in the preceding Clause D, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a lipid-modified mutant peptide. Clause D98. Any method described in the preceding Clause D, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of a lipidized linear peptide. Clause D99. Any method described in the preceding Clause D, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of the lipid-modified mutant peptide. Clause D100. The method according to any one of Clauses D1 to D99, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the lipidized linear peptide is not side-chain modified. Clause D101. The method, peptide for use or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipidized linear peptide, which is not modified, as described in any one of Clauses D1 to D99. Clause E1. The peptide has the sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of a linear peptide containing a salt thereof, or a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof (wherein X2 is P, X3 is something other than V), as described in any one of Clauses 1 to 4. Clause E2. The method described in Clause E1, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein all residues of the peptide skeleton are connected only by peptide bonds. Clause E3. The method described in Clause E1 or E2, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises 25 or fewer amino acid residues in the backbone. Clause E4. The method described in Clause E3, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the linear peptide, variant, or salt comprises 20 or fewer amino acid residues in the backbone, for example, 20 amino acid residues in the backbone. Clause E5. The method described in Clause E4, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises 15 or fewer amino acid residues in the backbone, for example, 15 amino acid residues in the backbone. Clause E6. The method described in Clause E5, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises 12 or fewer amino acid residues in the backbone, for example, 12 amino acid residues in the backbone. Clause E7. The method described in Clause E6, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises 11 or fewer amino acid residues in the backbone. Clause E8. The linear peptide, variant, or salt comprises at least seven amino acid residues in the skeleton, for example, the method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the linear peptide, variant, or salt comprising at least seven amino acid residues in the skeleton, for example, the peptide for use or a pharmaceutically acceptable salt thereof comprising seven amino acid residues in the skeleton, as described in any one of Clauses E1 to E7. Clause E9. The linear peptide, variant, or salt comprising at least eight amino acid residues in the skeleton, for example, the method described in Clause E8, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use comprising eight amino acid residues in the skeleton. Clause E10. The linear peptide, variant, or salt comprising, for example, at least nine amino acid residues in the skeleton, the method described in Clause E9, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use comprising the nine amino acid residues in the skeleton. Clause E11. The method according to Clause E10, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises at least 10 amino acid residues in the backbone, for example, the 10 amino acid residues in the backbone. Clause E12. The method according to Clause E11, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises at least 11 amino acid residues in the backbone. Clause E13. The method described in Clause E12, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises 11 amino acid residues in the backbone. Clause E14. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses E8 to E13, comprising a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 52 or a salt thereof. Clause E15. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a method according to any one of the clauses E8 to E13, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 53 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause E16. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. Alternatively, a method according to any one of the clauses E9 to E13, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 54 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause E17. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses E9 to E13, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 55 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause E18. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses E9 to E13, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 56 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause E19. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses E10 to E13, comprising a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 57 or a salt thereof. Clause E20. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses E10 to E13, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 58 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause E21. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses E10 to E13, comprising a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 59 or a salt thereof. Clause E22. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses E11 to E13, comprising a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 60 or a salt thereof. Clause E23. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 61 or a salt thereof, as described in any one of the clauses E11 to E13. Clause E24. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of the clauses E12 to E13, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 62 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause E25. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses E1 to E24, wherein X1 represents M. Clause E26. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses E1 to E24, wherein X1 represents K. Clause E27. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses E1 to E25, wherein X2 represents P. Clause E28. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses E1 to E25, wherein X2 represents D. Clause E29. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses E1 to E25, wherein X2 represents Q. Clause E30. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses E1 to E25, wherein X2 represents K. Clause E31. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses E1 to E25, wherein X2 represents G. Clause E32. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses E1 to E31, wherein X3 represents I. Clause E33. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses E1 to E31, where X3 represents L. Clause E34. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses E1 to E31, wherein X3 represents A. Clause E35. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses E1 to E31, wherein X3 represents T. Clause E36. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses E1-E26 or E28-E31, in which X3 represents V. Clause E37. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses E1 to E36, wherein X4 represents E. Clause E38. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses E1 to E36, wherein X4 represents A. Clause E39. The linear peptide, variant, or salt comprises any one sequence of SEQ ID NOs: 1-10 and 16-39 or a salt thereof, or a conservatively substituted variant of any one sequence of SEQ ID NOs: 1-10 and 16-39 or a salt thereof, for example, consisting of any one sequence of SEQ ID NOs: 1-10 and 16-39 or a salt thereof, or consisting of any one conservatively substituted variant of any one sequence of SEQ ID NOs: 1-10 and 16-39 or a salt thereof, as described in any one of Clauses E12-E13, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause E40. The linear peptide, variant, or salt comprises the sequence of SEQ ID NO: 1 or a salt thereof, or comprises a conservatively substituted variant of SEQ ID NO: 1 or a salt thereof, for example, consisting of the sequence of SEQ ID NO: 1 or a salt thereof, or consisting of a conservatively substituted variant of SEQ ID NO: 1 or a salt thereof, as described in any one of Clauses E12 to E13, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause E41. The method described in any one of Clauses E1 to E40, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the variant or salt thereof comprises two conservative substitutions. Clause E42. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X1 at position -2, for example, a substitution by E, N, Q, R, T, I, L, or V. Clause E43. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause E44. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 0, for example, A, D, G, K, Q, or V, in particular G, K, Q, or V. Clause E45. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause E46. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X3 at position 2, for example, by D, E, F, G, H, K, M, N, P, Q, or W, in particular by substitution by D, E, F, G, H, K, M, N, P, Q, or W. Clause E47. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of E at position 3, for example, A, D, G, K, Q, or V, in particular G, K, Q, or V. Clause E48. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause E49. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular G, K, Q, T, or V. Clause E50. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of E at position 6, for example, by A, D, G, K, Q, or V. Clause E51. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of D at position 7, for example, a substitution by A, E, G, H, N, V, or Y. Clause E52. The method described in any one of Clauses E1 to E41, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of V at position 8, for example, substitution by D, E, I, L, or M. Clause E53. The method described in any one of Clauses E41 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X1 at position -2, for example, a substitution by E, N, Q, R, T, I, L, or V. Clause E54. The method described in any one of Clauses E41 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause E55. The method described in any one of Clauses E41 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 0, for example, A, D, G, K, Q, or V, in particular G, K, Q, or V. Clause E56. The method described in any one of Clauses E41 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use of the variant or salt thereof, comprising substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause E57. The method described in any one of Clauses E41 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X3 at position 2, for example, D, E, F, G, H, K, M, N, P, Q, or W, in particular D, E, F, G, H, K, M, N, P, Q, or W. Clause E58. The method described in any one of Clauses E41 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of E at position 3, for example, A, D, G, K, Q, or V, in particular G, K, Q, or V. Clause E59. The method described in any one of Clauses E41 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause E60. The method described in any one of Clauses E41 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular G, K, Q, T, or V. Clause E61. The method described in any one of Clauses E41 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of E at position 6, for example, by A, D, G, K, Q, or V. Clause E62. The method described in any one of Clauses E41 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of D at position 7, for example, a substitution by A, E, G, H, N, V, or Y. Clause E63. The method described in any one of Clauses E41 to E52, wherein the variant or salt thereof comprises a substitution of V at position 8, for example, by D, E, I, L, or M, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause E64. The method described in any one of Clauses E42 to E52, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises one conservative substitution. Clause E65. The method described in any one of Clauses E1 to E40, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use wherein the peptide is a linear peptide or a salt thereof. Clause E66. The method described in any one of Clauses E1 to E65, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt is acetylated at its N-terminus. Clause E67. The linear peptide, variant, or salt not modified at the N-terminus, the method described in any one of Clauses E1 to E65, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause E68. The method described in any one of Clauses E1 to E67, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide, variant, or salt is amidated at the C-terminus. Clause E69. The method described in any one of Clauses E1 to E67, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the linear peptide, variant, or salt which is not modified at the C-terminus. Clause E70. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 1 or a salt thereof. Clause E71. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 2 or a salt thereof. Clause E72. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 3 or a salt thereof. Clause E73. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 4 or a salt thereof. Clause E74. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 5 or a salt thereof. Clause E75. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 6 or a salt thereof. Clause E76. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 7 or a salt thereof. Clause E77. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 8 or a salt thereof. Clause E78. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 9 or a salt thereof. Clause E79. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 10 or a salt thereof. Clause E80. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 16 or a salt thereof. Clause E81. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 17 or a salt thereof. Clause E82. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 18 or a salt thereof. Clause E83. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 19 or a salt thereof. Clause E84. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 20 or a salt thereof. Clause E85. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 21 or a salt thereof. Clause E86. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 22 or a salt thereof. Clause E87. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 23 or a salt thereof. Clause E88. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 24 or a salt thereof. Clause E89. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 25 or a salt thereof. Clause E90. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 26 or a salt thereof. Clause E91. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 27 or a salt thereof. Clause E92. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 28 or a salt thereof. Clause E93. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 29 or a salt thereof. Clause E94. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 30 or a salt thereof. Clause E95. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises SEQ ID NO: 31 or a salt thereof. Clause E96. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 32 or a salt thereof. Clause E97. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 33 or a salt thereof. Clause E98. The method described in Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide or salt comprises Sequence ID No. 34 or a salt thereof. Clause E99. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 35 or a salt thereof. Clause E100. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 36 or a salt thereof. Clause E101. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 37 or a salt thereof. Clause E102. The method according to Clause E1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 38 or a salt thereof. Clause E103. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, according to any one of Clauses E1 to E102, wherein the salt is a pharmaceutically acceptable salt. Clause E104. Any method described in the preceding Clause E, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a linear peptide. Clause E105. Any method described in the preceding Clause E, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a mutant peptide. Clause E106. Any method described in the preceding Clause E, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of the linear peptide. Clause E107. Any method described in the preceding Clause E, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of the variant peptide. Clause E108. The method according to any one of Clauses E1 to E107, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide is not side-chain modified. Clause E109. The method described in any one of Clauses E1 to E107, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the linear peptide which is not modified. Clause F1. The peptide contains 10 or fewer amino acid residues in its backbone, and its sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of a linear peptide comprising a salt thereof or a conservatively substituted variant of SEQ ID NO: 51 or a salt thereof, as described in any one of Clauses 1 to 28. Clause F2. The method described in Clause F1, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein all residues of the peptide skeleton are connected only by peptide bonds. Clause F3. The method according to Clause F1 or F2, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises six amino acid residues in the skeleton. Clause F4. The method according to Clause F1 or F2, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises seven amino acid residues in the skeleton. Clause F5. The method according to Clause F1 or F2, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises eight amino acid residues in the backbone. Clause F6. The method according to Clause F1 or F2, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises nine amino acid residues in the backbone. Clause F7. The method according to Clause F1 or F2, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt comprises 10 amino acid residues in the skeleton. Clause F8. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses F1, F2, or F4-F7, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 52 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F9. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses F1, F2, or F4-F7, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 53 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F10. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses F1, F2, or F5-F7, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 54 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F11. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses F1, F2, or F5-F7, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 55 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F12. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses F1, F2, or F6-F7, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 56 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F13. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses F1, F2, F6, or F7, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 57 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F14. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses F1, F2, F6, or F7, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 58 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F15. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses F1, F2, F6, or F7, comprising a salt thereof, or a conservatively substituted variant of Sequence ID No. 59 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F16. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X1 represents M and K. X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses F1, F2, or F7, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 60 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F17. The linear peptide, variant, or salt has the following sequence: [ka] (Here: X2 represents P, D, Q, K, and G. X3 represents I, L, A, T, V, X4 represents E and A. A method according to any one of clauses F1, F2, or F7, comprising a salt thereof, or a conservatively substituted variant of SEQ ID NO: 61 or a salt thereof, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F18. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F17, wherein X1 represents M. Clause F19. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F17, wherein X1 represents K. Clause F20. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F19, wherein X2 represents P. Clause F21. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F19, wherein X2 represents D. Clause F22. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F19, where X2 represents Q. Clause F23. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F19, wherein X2 represents K. Clause F24. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F19, wherein X2 represents G. Clause F25. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses F1 to F24, wherein X3 represents I. Clause F26. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F24, wherein X3 represents L. Clause F27. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses F1 to F24, wherein X3 represents A. Clause F26. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F24, wherein X3 represents T. Clause F29. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F24, wherein X3 represents V. Clause F30. X4 represents E, the method described in any one of Clauses F1 to F29, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F31. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use as described in any one of Clauses F1 to F29, wherein X4 represents A. Clause F32. The method according to any one of Clauses F1 to F31, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide, variant, or salt comprises any one sequence of SEQ ID NOs. 40 to 42 or a salt thereof, or a conservatively substituted variant of any one sequence of SEQ ID NOs. 40 to 42 or a salt thereof. Clause F33. The method according to Clause F32, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide, variant, or salt comprises any one sequence of SEQ ID NOs. 40-42 or a salt thereof, or a conservatively substituted variant of any one sequence of SEQ ID NOs. 40-42 or a salt thereof. Clause F34. The method according to any one of Clauses F1 to F33, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the variant or salt thereof comprises two conservative substitutions. Clause F35. The method described in any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X1 at position -2, for example, a substitution by E, N, Q, R, T, I, L, or V. Clause F36. The method described in any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause F37. The method described in any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 0, for example, A, D, G, K, Q, or V, in particular G, K, Q, or V. Clause F38. The method described in any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause F39. The method described in any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X3 at position 2, for example, by D, E, F, G, H, K, M, N, P, Q, or W, in particular by D, E, F, G, H, K, M, N, P, Q, or W. Clause F40. The method described in any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of E at position 3, for example, A, D, G, K, Q, or V, in particular G, K, Q, or V. Clause F41. The method described in any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause F42. The method according to any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular G, K, Q, T, or V. Clause F43. The method according to any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of E at position 6, for example, by A, D, G, K, Q, or V. Clause F44. The method described in any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes a substitution of D at position 7, for example, by A, E, G, H, N, V, or Y. Clause F45. The method described in any one of Clauses F1 to F34, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of V at position 8, for example, substitution by D, E, I, L, or M. Clause F46. The method described in any one of Clauses F34 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of X1 at position -2, for example, a substitution by E, N, Q, R, T, I, L, or V. Clause F47. The method described in any one of Clauses F34 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of T at position-1, for example, A, K, M, N, R, or S, in particular a substitution by A, K, M, N, or R. Clause F48. The method described in any one of Clauses F34 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 0, for example, by A, D, G, K, Q, or V, in particular by substitution by G, K, Q, or V. Clause F49. The method described in any one of Clauses F34 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of X2 at position 1, for example, A, C, E, H, L, M, N, R, S, T, V, or Y, in particular A, E, H, L, M, N, R, T, V, or Y. Clause F50. The method described in any one of Clauses F34 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X3 at position 2, for example, by D, E, F, G, H, K, M, N, P, Q, or W, in particular by D, E, F, G, H, K, M, N, P, Q, or W. Clause F51. The method described in any one of Clauses F34 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof includes substitution of E at position 3, for example, by A, D, G, K, Q, or V, in particular by G, K, Q, or V. Clause F52. The method described in any one of Clauses F34 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises a substitution of H at position 4, for example, by D, L, N, P, Q, R, or Y. Clause F53. The method described in any one of Clauses F34 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises substitution of X4 at position 5, for example, G, K, Q, S, T, or V, in particular G, K, Q, T, or V. Clause F54. The method described in any one of Clauses F34 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of E at position 6, for example, substitution by A, D, G, K, Q, or V. Clause F55. The method described in any one of Clauses F34 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the variant or salt thereof, comprising substitution of D at position 7, for example, substitution by A, E, G, H, N, V, or Y. Clause F56. The method described in any one of Clauses F34 to F45, wherein the variant or salt thereof comprises a substitution of V at position 8, for example, by D, E, I, L, or M, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause F57. The method according to any one of Clauses F35 to F45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the variant or salt thereof comprises one conservative substitution. Clause F58. The method according to any one of Clauses F1 to F57, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide, variant, or salt is acetylated at the N-terminus. Clause F59. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the linear peptide, variant, or salt which is not modified at the N-terminus, as described in any one of Clauses F1 to F57. Clause F60. The method according to any one of Clauses F1 to F59, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide, variant, or salt is amidated at the C-terminus. Clause F61. The method described in any one of Clauses F1 to F59, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the linear peptide, variant, or salt which is not modified at the C-terminus. Clause F62. The method according to any one of Clauses F1 to F33, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a linear peptide. Clause F63. The method according to Clause F1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 40 or a salt thereof. Clause F64. The method according to Clause F1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 41 or a salt thereof. Clause F65. The method according to Clause F1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the linear peptide or salt comprises Sequence ID No. 42 or a salt thereof. Clause F66. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use, according to any one of Clauses F1 to F65, wherein the salt is a pharmaceutically acceptable salt. Clause F67. Any method described in the preceding Clause F, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a linear peptide. Clause F68. Any method described in the preceding Clause F, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the peptide is a mutant peptide. Clause F69. Any method described in the preceding Clause F, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of the linear peptide. Clause F70. Any method described in the preceding Clause F, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the peptide is a pharmaceutically acceptable salt of the mutant peptide. Clause F71. The method according to any one of Clauses F1 to F70, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use wherein the linear peptide is not side-chain modified. Clause F72. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the linear peptide in which the linear peptide is not modified, as described in any one of Clauses F1 to F70. Clause G1. The lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or any salt thereof can increase BDNF levels, as described in any one of Clauses 1-4, A1-A98, B1-B99, C1-C70, D1-D101, E1-E109, or F1-F72, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause G2. The method described in Clause G1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or a salt thereof can increase BDNF levels by at least 20% between 0 and 24 hours after administration in the assay of Example 10. Clause H1. The lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or any salt thereof can increase phospho-CREB(Ser133) levels, as described in any one of Clauses 1-4, A1-A98, B1-B95, C1-C70, D1-D101, E1-E109, or F1-F72, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use thereof. Clause H2. The method described in Clause H1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or a salt thereof can increase the CREB level by at least 30% between 0 and 24 hours after administration in the assay of Example 10. Clause I1. The lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or any salt thereof can increase PGC1a levels, as described in any one of Clauses 1-4, A1-A99, B1-B95, C1-C70, D1-D101, E1-E109, or F1-F72, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use thereof. Clause I2. The method described in Clause I1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or a salt thereof can increase the PGC1a level by at least 30% between 0 and 24 hours after administration in the assay of Example 10. Clause J1. The lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or any salt thereof can increase TFEB levels, as described in any one of Clauses 1-4, A1-A99, B1-B95, C1-C70, D1-D101, E1-E109, or F1-F72, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use thereof. Clause J2. The method described in Clause J1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or a salt thereof can increase the TFEB level by at least 30% between 0 and 24 hours after administration in the assay of Example 10. Clause K1. The lipidized cyclic peptide, cyclic peptide, lipidized linear peptide, linear peptide, any variant thereof, and / or any salt thereof can reduce NfL levels, as described in any one of Clauses 1-4, A1-A99, B1-B95, C1-C70, D1-D101, E1-E109, or F1-F72, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use thereof. Clause K2. The method described in Clause K1, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or a salt thereof can reduce the NfL level by at least 10% in the assay of Example 31. Clause L1. Any method described in the preceding Clause, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or a salt thereof having an improved ability to increase BDNF, PGC1a, TFEB, and / or phospho-CREB(Ser133) compared to CPX. Clause L2. The lipid-containing cyclic peptide, cyclic peptide, lipid-containing linear peptide, linear peptide, any variant thereof, and / or any salt thereof, compared to CPX, particularly in the brain, improved t 1 / 2 AUC, or C max A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or any of the methods described in the preceding clauses, having any of the above. Clause L3. The lipid-containing cyclic peptide, cyclic peptide, lipid-containing linear peptide, linear peptide, any variant thereof, and / or any salt thereof, compared to CPX, show improved t in the brain. 1 / 2 A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or any of the methods described in the preceding clauses, having any of the above. Clause L4. Any method described in the preceding Clause, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or a salt thereof having the ability to increase BDNF, PGC1a, TFEB and / or phospho-CREB(Ser133) to at least the same level as CLP1. Clause L5. The lipid-containing cyclic peptide, cyclic peptide, lipid-containing linear peptide, linear peptide, any variant thereof, and / or a salt thereof is at least equivalent to CLP1, particularly in the brain. 1 / 2 AUC, or C max A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or any of the methods described in the preceding clauses, having any of the above. Clause L6. The lipid-containing cyclic peptide, cyclic peptide, lipid-containing linear peptide, linear peptide, any variant thereof, and / or a salt thereof is at least equivalent to CLP1, particularly in the brain. 1 / 2 A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or any of the methods described in the preceding clauses, having any of the above. Clause L7. Any method described in the preceding clause, peptide or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use of the lipid-modified cyclic peptide, cyclic peptide, lipid-modified linear peptide, linear peptide, any variant thereof, and / or salt thereof, which exhibit a lack of fibrillation at pH 6.5 and 7.5, preferably at pH 4.5, pH 6.5, and pH 7.5 (e.g., by the method of Example 5). Clause L8. The lipid-containing cyclic peptide, cyclic peptide, lipid-containing linear peptide, linear peptide, any variant thereof, and / or a salt thereof, are allowed to stand for at least 1 hour, preferably at least 4 hours, and in particular at least 8 hours. 1 / 2Any method described in the preceding clause, demonstrating (for example, by the method of Example 9), a peptide or a pharmaceutically acceptable salt thereof for use, a pharmaceutical composition for use, or use. Clause L9. The lipid-containing cyclic peptide, cyclic peptide, lipid-containing linear peptide, linear peptide, any variant thereof, and / or a salt thereof, in the brain for at least 1 hour, preferably at least 4 hours, and in particular at least 8 hours. 1 / 2 The method described in Clause Q8, which demonstrates (for example, by the method of Example 9), a peptide or a pharmaceutically acceptable salt thereof for use, a pharmaceutical composition for use, or use. Clause M1. The method, peptide for use or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use described in any one of Clauses 1 to L9, wherein the disease or disorder of the ear or mastoid process is a disease or disorder accompanied by hearing loss or hearing impairment. Clause M2. The method described in Clause M1, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use of the hearing loss being sensorineural hearing loss. Clause M3. The method, peptide for use or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use described in Clause M1 or M2, wherein the hearing loss is acquired hearing loss. Clause M4. The hearing loss is congenital hearing loss, the method described in Clause M1 or M2, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use. Clause M5. The method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses M1 to M4, wherein the hearing loss is hereditary hearing loss. Clause M6. The method described in Clause M5, peptides for use or pharmaceutically acceptable salts thereof, pharmaceutical compositions for use, or use of the hereditary hearing loss being symptomatic hearing loss. Clause M7. The method described in Clause M6, a peptide or pharmaceutically acceptable salt thereof for use, a pharmaceutical composition for use, or use, wherein the syndrome is selected from Stickler syndrome, Waardenburg syndrome, branchio-otorenal syndrome, CHARGE syndrome, Treacher Collins syndrome, Usher syndrome, Pendred syndrome, Yabel-Lange-Nielsen syndrome, Alport syndrome, and X-linked congenital stape-fixation syndrome with perilymphatic spurt. Clause M8. The method described in Clause M5, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use of the hereditary hearing loss being non-symptomatic hearing loss. Clause M9. The method described in Clause M8, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use thereof, wherein the non-symptomatic hearing loss relates to a mutation in one or more genes selected from GJB2, GJB6, STRC, KCNQ4, TECTA, and POU3F4. Clause M10. The method, peptide for use or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use relating to mitochondrial disease, as described in any one of Clauses M1 to M5. Clause M11. The method described in Clause M10, peptides or pharmaceutically acceptable salts thereof, pharmaceutical compositions for use, or use thereof, wherein the mitochondrial disease is selected from mitochondrial encephalomyopathy, lactic acidosis and stroke-like seizures (MELAS), maternal inherited diabetes mellitus and hearing loss (MIDD), Kearns-Sayre syndrome (KSS), and myoclonus epilepsy and red rag fibers (MERRF). Clause M12. The method, peptide for use or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use described in any one of Clauses M1 to M11, wherein the hearing loss is auditory synaptopathy or neurological disorder. Clause M13. The method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use, for which the hearing loss is latent hearing loss, as described in any one of Clauses M1 to M12. Clause M14. If the disease or disorder of the ear or mastoid process is vestibular syndrome, the method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use described in Clause M1. Clause M15. The vestibular syndrome is Meniere's disease, the method described in Clause M14, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use thereof. Clause M16. The method described in Clause M14, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use of the vestibular syndrome being a vertigo syndrome. Clause M17. The method described in any one of Clauses 1 to M16, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the administration of the peptide results in hearing improvement. Clause M18. The method described in Clause M17, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use thereof, wherein the hearing improvement is measured using a pure-tone audiometry test. Clause M19. The method described in Clause M17 or M18, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use wherein the auditory improvement is measured using auditory brainstem response. Clause M20. The method described in any one of Clauses M17 to M19, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use wherein the hearing improvement is measured using otoacoustic emissions. Clause M21. The method, peptide for use or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use described in any one of Clauses M17 to M20, wherein the auditory improvement is an improvement in one or more of the speech detection threshold, speech recognition threshold, and / or word recognition score. Clause M22. The hearing improvement is measured using one or more of the following methods described in any one of Clauses M17 to M21: a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use. Clause M23. The method described in any one of Clauses 1 to M22, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the administration of the peptide increases the number of cochlear ribbon synapses. Clause M24. The method described in any one of Clauses 1 to M23, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the administration of the peptide increases the number of spiral ganglion neurons. Clause M25. The method described in any one of Clauses 1 to M24, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use which the administration of the peptide increases the number of inner hair cells and / or outer hair cells. Clause M26. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use, as described in any one of Clauses 1 to M25, for use in the treatment of therapies. Clause M27. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use, as described in any one of Clauses 1 to M25, for use in prevention. Clause M28. A method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use, as described in any one of Clauses 1 to M27, for use in human subjects. Clause M29. The method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses 1 to M28, wherein the human subject is under 2 years of age. Clause M30. The method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses 1 to M28, wherein the subject is between 2 and 17 years of age. Clause M31. The method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use described in any one of Clauses 1 to M28, wherein the human subject is between 18 and 65 years of age. Clause M32. The method described in any one of Clauses 1 to M28, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use of the human subject being 66 years of age or older. Clause M33. Any method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use of the aforementioned method, peptide or pharmaceutically acceptable salt thereof pharmaceutical composition for use, or use described in any of the preceding Clauses. Clause M34. The method described in Clause M33, peptides for use or pharmaceutically acceptable salts thereof, pharmaceutical compositions for use, or use relating the cochlear synaptopathy to aging, sensorineural hearing loss, noise-induced hearing loss. Clause M35. The method described in Clause M33, the peptide for use or a pharmaceutically acceptable salt thereof, the pharmaceutical composition for use, or the use thereof, if the cochlear synaptopathy is associated with an inflammatory or neurodegenerative disorder, such as Huntington's disease, Parkinson's disease, or Alzheimer's disease. Clause M36. Any method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use of the ear or mastoid process if the disease or disorder is age-related hearing loss as described in the preceding Clause. Clause M36. Any method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use, described in any of the preceding clauses, in which the hearing loss is caused by noise exposure. Clause M37. Any method, peptide for use or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use described in any of the preceding clauses, which determines that the hearing loss is due to exposure to an ototoxic drug. Clause M38. Any method, peptide or pharmaceutically acceptable salt thereof for use, pharmaceutical composition for use, or use which the noise-induced speech inhalation (SIN) test is improved compared to an untreated subject. Clause M39. Noise-induced word audibility test (WIN) is improved compared to untreated subjects, by the method described in Clause M38, by a peptide or pharmaceutically acceptable salt thereof for use, by a pharmaceutical composition for use, or by any use. Clause M40. Any method described in the preceding clause, peptide for use or pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use that increases the absolute OAE amplitude compared to when untreated. Clause M41. Any method described in the preceding clause, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use thereof, wherein the peptide is cyclized and the backbone of the peptide is connected only by peptide bonds. Clause M42. Any method described in the preceding clause, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use wherein all of the aforementioned residues in the cyclic peptide are intracyclic.

[0167] The present invention will also be described in more detail with reference to the following embodiments, but will not be limited thereto. The embodiments may be modified without departing from the scope of the invention.

[0168] Furthermore, as used herein and in the appended claims, the singular forms "a," "an," and "the" include multiple references unless the content explicitly indicates otherwise. Thus, for example, a reference to "peptide" includes two or more such peptides, etc.

[0169] All publications, patents, and patent applications cited herein, whether above or below, are incorporated herein by reference in their entirety. [Examples]

[0170] (Examples) (statistics) Unless otherwise specified, significance was assessed using a two-tailed Student's t-test. Error bars indicate: * p<0.05, ** p<0.01, *** p<0.001, **** This shows an SEM with p<0.0001.

[0171] (Example 1: Peptide synthesis) The linear peptide was synthesized using standard Fmoc (fluorenylmethyloxycarbonyl) chemistry.

[0172] (Preparation of resin) Fmoc-Pro-OH (0.2 mmol, 1 equivalent) and N,N-diisopropylethylamine (DIPEA) (0.14 mL, 4 equivalents) were added to 2-CTC resin (0.2 mmol, 1.00 equivalent, less than 1.05 mmol / g) in dichloromethane (DCM) (10 mL). The mixture was stirred under N2 at 20°C for 2 hours, then methanol (MeOH) (0.5 mL) was added and stirred for a further 30 minutes with N2 bubbling. The resin was washed three times with dimethylformamide (DMF) (15 mL).

[0173] (deprotection) Fmoc removal was performed by adding 20% ​​piperidine in DMF (15 mL) to the resin and stirring under N2 for 30 minutes. The resin was washed four times (15 mL) with DMF and filtered.

[0174] (Coupling) Sequential amino acid coupling was performed by adding a solution of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) (2.85 equivalents), DIPEA (6 equivalents), and Fmoc-protected amino acid (3 equivalents) in DMF (5 mL) to the resin and stirring at 20°C for 30 minutes under N2. The resin was then washed four times with DMF (15 mL). The Fmoc deprotection and coupling steps were repeated for each subsequent amino acid until the desired peptide sequence was obtained. The resin was then washed four times with dimethylformamide (DMF) (15 mL). The Fmoc removal and coupling steps were repeated until the desired peptide sequence was obtained. The resulting side-chain protected, resin-bound linear peptide was used directly in the next step.

[0175] The Fmoc-protected amino acid building blocks used were: Fmoc-Ala-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Cys(Trt)-OH, Fmoc-Gln(Trt)-OH, FmocGlu(OtBu)-OH, Fmoc-Gly-OH, Fmoc-His(Trt)-OH, Fmoc-Ile-OH, Fmoc-Leu-OH, Fmoc-Lys(Boc)OH, Fmoc-Met-OH, Fmoc-Phe-OH, Fmoc-Pro-OH, Fmoc-Ser(tBu)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Tyr(tBu)-OH, and Fmoc-L-Val-OH. Unless otherwise specified, the natural L-form of the amino acids was used. Lipid attachment to lysine residues was performed using orthogonally protected Lys(Dde-Lys(Fmoc)-OH), in which Dde was positioned on the α-amine and Fmoc was positioned on the side-chain amine. After coupling the protected Lys, Fmoc was first removed, and then the lipid was coupled to the resulting exposed amine. Subsequently, Dde was removed, and the peptide chain was extended using Fmoc chemistry as usual.

[0176] (Example 2: Peptide cleavage, cyclization, and purification) After the final amino acid coupling and Fmoc removal, the resin from Example 1 was washed five times with DMF and three times with MeOH, and dried under vacuum. To generate cyclic peptides, the peptide resin was then treated with a cleavage cocktail (1% trifluoroacetic acid (TFA) / 99% DCM) (15 mL) for 15 minutes, and the peptide-containing TFA-DCM mixture was recovered. The cleavage was repeated three times. For the linear peptides, these were cleaved and deprotected using a strong acid (95% TFA). For the cyclic peptides, the peptides (in 1% TFA / 99% DCM) were diluted in DCM (200 mL) together with 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate (TBTU) (2 equivalents), 1-hydroxybenzotriazole hydrate (HOBT) (2 equivalents), and DIPEA (6 equivalents) to couple the head of the peptide to the tail. The mixture was stirred at 20°C for 1 hour. Cyclization was monitored by LC-MS.

[0177] After stirring, the mixture was washed twice with 1M hydrochloric acid (HCl) (30 mL) and dried under reduced pressure. 5 mL of cleavage buffer (92.5% TFA / 2.5% 3-mercaptopropionic acid / 2.5% triisopropylsilane / 2.5% H2O) was added to a flask containing the side-chain protected cyclic peptide, and the mixture was stirred at 20°C for 2 hours. The peptide was precipitated with ice-cold tert-butyl methyl ether (40 mL), centrifuged (at 3000 rpm for 2 minutes), and washed twice with ice-cold tert-butyl methyl ether (40 mL). The crude peptide was dried under vacuum for 2 hours, purified by preparative HPLC, and the target peptide fraction was freeze-dried to obtain a white solid.

[0178] Preparative HPLC method: (System: Gilson GX-281; ​​Column: Gemini, C18, 110 Å, 5 μm or Luna, C18, 100 Å, 10 μm; Gradient: Gradient run time 50 min; 0-50 min 7-37% B; Flow rate: 20 mL / min; Column temperature: 30 °C; Diode array: 220 / 254 nm; Solvent A: 0.075% TFA in water; Solvent B: Acetonitrile).

[0179] Qualitative analysis of the peptides was performed by HPLC and LC-MS (see Figure 1).

[0180] HPLC: Column: (Gemini C18, 110 Å, 5 μm, 150 × 4.6 mm; Gradient: Gradient run time 20 min; 0.00~20.00 min 15~45% B, 20.10~23.00 min 95% B, 23.00~23.10 min 95~15% B, 23.10~28.00 min 15% B; Flow rate: 1.0 mL / min; Diode array, 220 / 254 nm; Column temperature: 30 °C; Solvent A: 0.1% TFA in water; Solvent B: 0.075% TFA in acetonitrile).

[0181] LC-MS method for the final product: (System: Agilent Infinity II 1260 HPLC series; Column: Xbridge C18, 130 Å, 3.5 μm, 2.1 × 30 mm; Detector: Agilent LCMS (G6125C), single quadrupole TIC scan; Scan range: m / z min 100, m / z max 2000, positive mode, electrospray; Gradient: Gradient run time 1 min; 0.00~1.00 min 10~80%B; Column washing and equilibration; 1.00~1.01 min 80~95%B, 1.01~1.60 min 95%B, 1.60~1.61 min 95~10%B, 1.61~2.00 min 10%B; Flow rate: 1.2 mL / min; Diode array: 215 or 220 nm; column temperature: room temperature; solvent A: 0.1% TFA in water; solvent B: 0.075% TFA in acetonitrile).

[0182] (result) A summary of the LC-MS and HPLC purity data is shown in the table below, along with the exemplary chromatograms and mass spectra of CLP1 shown in Figures 1A and 1C. Table 4 - Summary of peptide HPLC purification and MS characterization [Table 4] TIFF2026529639000186.tif221170TIFF2026529639000187.tif188170 * Monoisotopic

[0183] (Example 3: CLP1 treatment results in an increase in CREB target genes) SorCS2 has recently been shown to play a crucial role in BDNF / TrkB signaling by being essential for the activation of downstream kinases (Glerup, 2016). The primary mediator of the neurotrophin response to BDNF is the activation of the transcription factor CREB (Finkbeiner, 1997; Walton, 2000; Benito, 2010; Sakamoto, 2011). CREB activation is well known to improve neuronal survival, synapse formation, and growth. This crucial mediator is the production of BDNF itself by CREB (Tao, 1998), thereby establishing a positive feedback loop. Similarly, CREB activation has been described as inducing mitochondrial biosynthesis through the upregulation of the master regulator PGC1a (Wu, 2006; Kang, 2017). Indeed, CPX, a cyclized peptide mimetic of the SorCS2 receptor fragment, increases BDNF levels in wild-type neurons after 4 hours of stimulation (WO2022029281). Since CLP1 is a cyclized lipid-containing peptide mimetic of the SorCS2 receptor fragment, which is important for BDNF signaling, we evaluated whether CLP1 treatment results in increased BDNF and PGC1a production in wild-type neurons as a result of CREB activation. We compared the effects of the cyclized and stabilized lipid-containing peptide CLP1 with those of the cyclized peptide CPX.

[0184] Cortical neurons were isolated from p0 wild-type mice and seeded at a density of 200,000 per well (24-well tray). In vitro, after 7 days, neurons were stimulated with 1 μM CLP1 or CPX in neurobasal A 15 medium and incubated at 37°C and 5% CO2 for 8, 16, or 24 hours. Subsequently, neurons were lysed in RIPA lysis buffer containing the cOmplete cocktail protease inhibitor. BDNF and PGC1a levels were analyzed by Western blotting normalized to β-actin.

[0185] As shown in Figures 2A and 2B, CLP1 significantly increased BDNF by 180% (p=0.0174) and PGC1a by 611% (p<0.0001) in the evaluated CREB downstream target genes after 24 hours of stimulation. CPX did not increase either BDNF or PGC1a levels, likely due to the fact that its effect is induced before the evaluation time. This indicates an extension of signaling by CLP1 compared to CPX.

[0186] (Example 4: CLP1 removes soluble mHTT from fibroblasts derived from Huntington's disease patients) Autophagy is the process of removing misfolded proteins, aggregates, or damaged organelles. In addition to driving mitochondrial biosynthesis, PGC1a has been shown to promote lysosome biosynthesis through the regulation of TFEB (the master regulator of lysosome biosynthesis) (Ghosh, 2015; Lynch, 2020). To account for the upregulation of PGC1a and the regulation of TFEB, we evaluated the CLP1-induced reduction of mHTT (mutant huntingtin) protein expressed from disease-causing genes in HD. For comparison of efficacy, we also included CPX (WO2022029281), which has been previously shown to reduce mutant HTT levels. Patient-derived fibroblasts GM04476 (from Coriell Biobank) were seeded in 96-well plates at a rate of 30,000–50,000 cells per well. The following day, cells were treated with 1 μM CLP1 or CPX and incubated at 37°C and 5% CO2 for 24 hours. The cells were then lysed with RIPA lysis buffer containing the cOmplete cocktail protease inhibitor. Total huntingtin levels were analyzed using the antibody mab2166 (Sigma-Aldrich), and mutant huntingtin levels were measured using an antibody (MW1 ab) that detects only mutant alleles by Western blotting. These levels were normalized relative to β-actin. As shown in Figures 3A and 3B, both CLP1 and CPX reduced mutant huntingtin levels to 50% (p=0.0048) and 75% (p=0.0209), respectively, while reducing total huntingtin levels (mutant and normal alleles) to approximately 65% ​​(p=0.0036) for CLP1 and 75% (p=0.0056) for CPX. This indicates that CLP1 specifically induces degradation of mutant huntingtin protein more than normal huntingtin protein, and that CLP1's potency is increased compared to CPX, thereby offering a valuable opportunity as a therapeutic agent for HD patients.

[0187] (Example 5: Chemical and physical stability of CLP1) To better understand the stability and chemical basis of CLP1 degradation, the chemical and physical stability of CLP1 in three buffer systems was evaluated. CLP1 solutions were prepared in three buffer systems with different pH values, and the samples were incubated at 40°C without agitation. Chemical stability was assessed by ULC-UV on the preparation day (t0) and after 2 weeks of incubation (t14). Physical stability was assessed by a thioflavin T (ThT) assay over 4 days with agitation at 40°C.

[0188] For each assay, the sample was dissolved to a peptide concentration of 1 mg / mL in either 25% acetonitrile (ACN) (for analytical standard solution) or one of three buffer systems (50 mM sodium acetate buffer, pH 4.5 (22.5 mM sodium acetate + 27.5 mM glacial acetic acid); 50 mM L-histidine buffer, pH 6.5; 50 mM sodium phosphate buffer, pH 7.5 (40.6 mM Na2HPO4 + 9.4 mM NaH2PO4)). All buffers were prepared in ultrapure water with an electrical resistivity of 18.2 MΩ·cm (Milli-Q® Reference A+ System, Merck). The samples were centrifuged at 13300 rpm (17000 g) for 10 minutes before ULC-UV measurement. For physical stability testing, the samples were filtered through a 0.22 μm cellulose filter (13φ, Frisenette) before preparing the ThT assay.

[0189] (UPLC-UV method for chemical stability assays) Column: Phenomenex Kinetex 1.7μm C18 100Å 150×2.1mm; Mobile phase A: Ultrapure water + 0.1% TFA; Mobile phase B: Acetonitrile + 0.1% TFA; Injection volume: 2μL CLP1; Flow rate: 0.3mL / min, Detection wavelength: 220°

[0190] (gradient) [Table 5]

[0191] (Setting up the plate reader for the ThT assay) Excitation wavelength: 450nm; Dichroic filter: 465nm; Emission wavelength: 486nm; Focal height: 3.5mm; Gain: 1000; Cycle count: 1000; Cycle time: 360 seconds; Number of flashes per well: 20; Shaking: 300rpm, 5 seconds on, 5 seconds off between cycles; Temperature: 40℃.

[0192] The results (Figures 4A-4C) show that the greatest degradation of CLP1 occurred at pH 4.5 (9% AUC decrease). CLP1 showed similarly good chemical stability at pH 6.5 and 7.5 (1% AUC decrease). Physical stability was assessed by ThT assay to evaluate fibrillation behavior over 96 hours. CLP1 showed good physical stability, not exhibiting fibrillation in any buffer system (Figures 4D-4G). Each line represents an individual replica.

[0193] (Example 6: CLP1 free fraction and stability) A crucial aspect of drug development is pharmacokinetics, including absorption, distribution, metabolism, and excretion (ADME). The stability of CLP1 was evaluated in both human and mouse plasma samples and mouse brain homogenate samples. Since CLP1 is stabilized by two amino acid substitutions compared to CPX, CPX was included as a reference in these stability assays. The stability of CLP1 was similarly evaluated in liver S9 fractions derived from mouse, dog, rat, human, and monkey. Brain binding (free fraction) in both mouse and human brain homogenates was also evaluated.

[0194] (Plasma stability) Frozen mouse or human plasma was thawed in a 37°C water bath before use. Plasma was centrifuged at 4000 rpm for 5 minutes to remove any clots (if present). Mouse or human plasma was incubated with 2 μM CLP1 or CPX, or 2 μM propantheline bromide (positive control for degradation), in a water bath at 37°C. At each time point, a stop solution (200 ng / mL tolbutamide and 200 ng / mL labetalol in MeOH) was added to precipitate the proteins. After mixing and centrifugation, the supernatant was used for LC-MS analysis. As shown in Figures 5A and 5B, CLP1 and CPX had half-lives (t) greater than 28.9 hours. 1 It had ( / 2). This indicates high plasma stability. % remaining = 100 × (PAR at specified incubation time / PAR at T0 time), where PAR is the peak area ratio of analyte to internal standard (IS), and the half-life is t 1 / 2 Calculated using =0.693k.

[0195] (Mouse brain stability) Frozen mouse brain homogenates were thawed in a 37°C water bath before use. The mouse brain homogenates were incubated with 1 μM CLP1 or CPX or 2 μM 7-ethoxycoumarin (positive control for degradation) in a water bath at 37°C. At each time point, stop solutions (200 ng / mL tolbutamide and 200 ng / mL labetalol in MeOH) were added to precipitate the proteins. After mixing and centrifugation, the supernatant was used for LC-MS analysis. As shown in Figure 5C, CLP1 had a half-life of 40.7 hours (t) compared to 28.9 hours for CPX. 1 It had / 2). This indicates high brain stability of CLP1, which is improved compared to CPX.

[0196] (Example 7: CLP1 metabolic stability in liver fraction) Since the majority of drug metabolism occurs in the liver, hepatic in vitro preparations can serve as a model for evaluating the metabolic stability of drugs. To investigate metabolic stability, the S9 fraction, which contains a mixture of unfractionated microsomes and cytosol with a wide variety of drug-metabolizing enzymes, is often used. Hepatic S9 fraction is commonly used as a preferred test system for in vitro ADME.

[0197] (Stability of liver segment S9) CLP1 was added to human liver S9, CD-1 mouse liver S9, Sprague-Dolly rat liver S9, Beagle dog liver S9, and cynomolgus monkey liver S9 solutions (1 mg protein / mL) in 100 mM potassium phosphate buffer to a final concentration of 1 μM. 7-Ethoxycoumarin (1 μM) was used as a positive control for clearance. The reaction was initiated by adding a cofactor regeneration system containing nicotinamide adenine dinucleotide phosphate (NADP) (1.3 mM), glucose 6-phosphate (G6P) (3.3 mM), glucose 6-phosphate dehydrogenase (G6PDH) (0.4 U / mL), uridine diphosphate glucuronic acid (UDPGA) (2.5 mM), 3'-phosphoadenosine-5'-phosphosulfate (PAPS) (0.1 mM), glutathione (GSH) (5 mM), and MgCl2 (3.3 mM) in 100 mM phosphate buffer. The reaction was carried out at different time points between 0 and 2 hours, and then terminated with stop solution. After shaking the plate and centrifugation, the supernatant was used for LC-MS analysis. As shown in Figure 6A (intrinsic clearance rate) and Figure 6C (% remaining), CLP1 has a very low clearance of <2.4 μL / min / mg in all species and a half-life of at least 289 minutes (t 1 T 1 / 2 was calculated as follows: T 1 / 2 = Ln2 / k e =0.693 / k e。Intrinsic clearance was calculated as follows: CLint(S9) = 0.693 / T1 / 2 / mg S9 protein / mL (where T1 / 2 is the half-life and CL is the intrinsic clearance). This indicates high metabolic stability. The 7-ethoxycoumarin control is shown in Figure 6B (intrinsic clearance rate) and Figure 6D (% remaining).

[0198] (Example 8: Free fraction of CLP1 in the brain) The measurement of total drug concentrations in the brain has limited correlation with their pharmacodynamic readout. To obtain a better correlation, drug concentrations in the brain must be corrected for the proportion of unbound and bound drugs. Therefore, the brain-free fraction of CLP1 in both human and mouse brain homogenates was evaluated. On the day of the experiment, the brain homogenates were thawed by running cold tap water. CLP1 and a control compound (propranolol) were dissolved in H2O to obtain a 10 mM stock solution in DMSO. A working solution (400 μM) was prepared by diluting 10 μL of the stock solution with 240 μL of H2O.

[0199] (Ultracentrifugation procedure) (Buffer preparation) Basic solutions were prepared by dissolving 14.2 g / L Na2HPO4 and 8.77 g / L NaCl in deionized water. Acidic solutions were prepared by dissolving 15.6 g / L NaH2PO4·2H2O and 8.77 g / L NaCl in deionized water. The basic solutions were titrated with the acidic solutions to pH 7.4 ± 0.1. Mouse brain was homogenized in buffer, loaded with (2 μM) CLP1 and a control compound (propranolol, 2 μM), and a working solution was prepared by diluting 6 μL of working solution with 1194 μL of blank matrix (no compound added). The DMSO concentration of the compound stock solution in the final solution was 0.5.

[0200] To prepare the time zero (T0) sample, which would be used for measuring residuals, 30 μL of loading matrix was transferred to a sample recovery plate (n=2). The sample was immediately added to 30 μL of buffer to obtain a final volume of 60 μL in each well with a plasma:buffer volume ratio (1:1, v:v). 480 μL of stop solution containing 60 μL of 4% H3PO4 in H2O and an internal standard was added. These were then stored at 2–8°C until further processing with the other samples. To prepare the protein-free sample (referred to as the F sample), which would be used for measuring unbound material, 400 μL aliquots of pre-incubated brain homogenate containing either CLP1 or a control compound were transferred to ultracentrifuge tubes (n=2) and ultracentrifuged at 37°C and 47000 × g (115000 rpm) for 2 hours to produce the F sample. At the end of ultracentrifugation, 30 μL of the sample was taken from the second layer (below the top layer) of the supernatant of sample F. To prepare the sample to be used for measuring unbound and residual material (referred to as sample T), a residual aliquot (n=1) of pre-incubated spike plasma was placed in the same incubator simultaneously with the ultracentrifugation and incubated at 37°C for 2 hours. The samples were transferred to a new 96-well plate. Equal volumes of the opposite blank matrix (buffer or plasma) were added to each sample to reach a final volume of 60 μL in each well with a plasma:buffer volume ratio of 1:1 (v:v). 480 μL of stop solution containing 60 μL of 4% H3PO4 in H2O and an internal standard was added to each sample. The mixtures were vortexed and centrifuged at 4000 rpm for approximately 20 minutes. Subsequently, 100 μL aliquots of the supernatant of all samples were taken for LC-MS / MS analysis.

[0201] The percentages of unbound, undiluted unbound, undiluted bound, and residual were calculated using the following formula: % unbound (free fraction) = 100 *F / T4.5; where F is the analyte concentration or analyte / internal standard peak area ratio of the protein-free sample after ultracentrifugation, and T4.5 is the analyte concentration or analyte / internal standard peak area ratio in the matrix after 4.5 hours of incubation. As shown in Figures 7A and B, CLP1 has a free fraction of 19% in mouse brain homogenate and 11% in human brain homogenate.

[0202] (Example 9: Pharmacokinetics of CLP1) The pharmacokinetics of CLP1 in wild-type mice were evaluated. Tenfold serial dilutions of CLP1 (2 mg / kg, 0.2 mg / kg, and 0.02 mg / kg) were subcutaneously injected (SC) into wild-type mice (male C57BL / 6J) in 4.38 mM L-His, 140 mM NaCl, 0.2% Tween-20, and 1500 IU hyaluronidase (pH 6.15). Concentrations in both plasma, whole brain, and cerebrospinal fluid were determined by LC-MS / MS at different time points from 1 to 24 hours.

[0203] (Plasma processing procedure) 40 μL aliquots of unknown sample, calibration standard, quality control, diluted quality control, single blank, and double blank were added to a 96-well plate. Each sample (except the double blank) was quenched with 160 μL of IS1 (internal standards in MeOH: 100 ng / mL each of labetalol, tolbutamide, verapamil, dexamethasone, glybride, and celecoxib) (the double blank sample was quenched with 160 μL of MeOH), and the mixtures were then vortex-mixed at 800 rpm for 10 minutes and centrifuged at 3220 g (4000 rpm) at 4°C for 15 minutes. 50 μL of the supernatant was transferred to another clean 96-well plate, centrifuged at 3220 g at 4°C for 5 minutes, and then injected directly for LC-MS / MS analysis.

[0204] (Brain processing procedure) Tissue homogenates were prepared by homogenizing tissue in a 5:5 volume (w:v) cold homogenization solution (MeOH / 15mM PBS (1:2, v:v)). 40 μL aliquots of unknown sample, calibration standard, quality control, diluted quality control, single blank, and double blank were added to 96-well plates; then 40 μL of male C57BL / 6J mouse plasma (EDTA-K2) was added and vortexed thoroughly (at least 5 minutes). Each sample (except the double blank) was quenched with 320 μL of IS1 (the double blank sample was quenched with 320 μL of MeOH), and the mixtures were then vortexed at 800 rpm for 10 minutes and centrifuged at 3220 g (4000 rpm) at 4°C for 15 minutes. 50 μL of supernatant was transferred to another clean 96-well plate, centrifuged at 3220 g at 4°C for 5 minutes, and then injected directly for LC-MS / MS analysis. The procedure was performed on ice.

[0205] (CSF processing procedure:) Equal volumes of plasma were added to the CSF sample and blank matrix, mixed thoroughly, and the protein was precipitated using a 1.5 mL tube. Aliquots of 20 μL of calibration standard, quality control and dilution quality control, single blank, and double blank samples were added to 1.5 mL tubes; each sample (except the double blank) was quenched with 400 μL of IS1 (the double blank was quenched with 400 μL of MeOH), the mixtures were then vortexed thoroughly (at least 15 seconds) and centrifuged at 12000 × g at 4°C for 15 minutes; all mixed unknown samples were quenched with 20-fold IS1, the mixtures were then vortexed thoroughly (at least 15 seconds) and centrifuged at 12000 × g at 4°C for 15 minutes; aliquots of 50 μL of supernatant were transferred to a 96-well plate and centrifuged at 3220 × g at 4°C for 5 minutes, after which the supernatant was injected directly for LC-MS / MS analysis. The procedure was performed on wet ice. The treatme...

Claims

1. A method for the treatment or prevention of disease or disorder of the ear or mastoid process, comprising the administration of a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide is: (i) Array: 【Chemistry 1】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: 【Chemistry 2】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X 2 If P, then X 3 ( is something other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: 【Transformation 3】 (Here: X 2 represents P, D, Q, K and G, X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: 【Chemistry 4】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: 【Transformation 5】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A linear peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X 2 If P, then X 3 is something other than V); or (vi) Containing 10 or fewer amino acid residues in the backbone, and in sequence: 【Transformation 6】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 The method described above.

2. A peptide or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of diseases or disorders of the ear or mastoid process, wherein the peptide is: (i) Array: 【Transformation 7】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: 【Transformation 8】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X 2 If P, then X 3 ( is something other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: 【Chemistry 9】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: 【Chemistry 10】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: 【Chemistry 11】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A linear peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X 2 If P, then X 3 is something other than V); or (vi) Containing 10 or fewer amino acid residues in the backbone, and in sequence: 【Chemistry 12】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 The peptide or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition for the treatment or prevention of diseases or disorders of the ear or mastoid process, comprising a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide is: (i) Array: 【Chemistry 13】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: 【Chemistry 14】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X 2 If P, then X 3 ( is something other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: 【Chemistry 15】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: 【Chemistry 16】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: 【Chemistry 17】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A linear peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X 2 If P, then X 3 is something other than V); or (vi) Containing 10 or fewer amino acid residues in the backbone, and in sequence: [Chemistry 18] (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 The pharmaceutical composition, which is the aforementioned pharmaceutical composition.

4. The use of a peptide or a pharmaceutically acceptable salt thereof in the manufacture of a pharmaceutical product for the treatment or prevention of a disease or disorder of the ear or mastoid process, wherein the peptide is: (i) Array: 【Chemistry 19】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Lipidized cyclic peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (ii) Array: 【Chemistry 20】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X 2 If P, then X 3 ( is something other than V); (iii) Containing 10 or fewer amino acid residues within the ring, and having the following sequence: 【Chemistry 21】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51; (iv) Array: 【Chemistry 22】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Lipidized linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51; (v) Array: 【Chemistry 23】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A linear peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X 2 If P, then X 3 is something other than V); or (vi) Containing 10 or fewer amino acid residues in the backbone, and in sequence: 【Chemistry 24】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) Linear peptides containing or containing a conservatively substituted variant of SEQ ID NO: 51 The aforementioned use.

5. The aforementioned peptide has the sequence: 【Chemistry 25】 (Here: X 2 These represent P, D, Q, K, and G. X 3 represents I, L, A, T, V, X 4 (This represents E and A.) Alternatively, a lipidized cyclic peptide comprising a conservatively substituted variant of SEQ ID NO: 51, the method according to any one of claims 1 to 4, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

6. The aforementioned lipid-modified cyclic peptide has the following sequence: 【Chemistry 26】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) The method according to claim 5, comprising, wherein the peptide comprises 15 or fewer amino acid residues in a ring, is cyclized, and all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

7. The aforementioned lipid-modified cyclic peptide has the following sequence: 【Chemistry 27】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 represents E and A) The method according to claim 6, comprising, wherein the peptide comprises 15 or fewer amino acid residues in a ring, is cyclized, and all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

8. The method according to claim 7, wherein the lipid of the lipidized cyclic peptide is C18DA-γGlu-OEG-OEG-, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

9. The aforementioned lipid-modified cyclic peptide Table 1 A method according to any one of claims 1 to 8, wherein the cyclic peptide is selected from, wherein the cyclic peptide is cyclized and wherein all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

10. The cyclic lipidized peptide is peptide CLP1: 【Chemistry 28】 (Here, * =C18DA-γGlu-OEG-OEG-, where the peptide is cyclized and all residues of the peptide skeleton are connected only by peptide bonds. The method according to claim 9, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

11. The cyclic lipidized peptide is peptide CLP1: 【Chemistry 29】 (Here, * =C18DA-L-γGlu-OEG-OEG-, where the peptide is cyclized and all residues of the peptide backbone are connected only by peptide bonds. The method according to claim 10, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

12. The cyclic lipidized peptide is peptide CLP1: 【Transformation 30】 (Here, * =C18DA-D-γGlu-OEG-OEG-, where the peptide is cyclized and all residues of the peptide skeleton are connected only by peptide bonds. The method according to claim 10, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

13. The aforementioned cyclic lipidized peptide is peptide CLP4: 【Chemistry 31】 (Here, * =C18DA-γGlu-OEG-OEG-, where the cyclic peptide is cyclized and all residues of the peptide backbone are connected only by peptide bonds. The method according to claim 9, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

14. The cyclic lipidized peptide is peptide CLP5: 【Chemistry 32】 (Here, * =C18DA-γGlu-OEG-OEG-, where the cyclic peptide is cyclized and all residues of the peptide backbone are connected only by peptide bonds. The method according to claim 9, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

15. The cyclic lipidized peptide is peptide CLP9: 【Transformation 33】 (Here, * =C18DA-γGlu-OEG-OEG-, where the cyclic peptide is cyclized and all residues of the peptide backbone are connected only by peptide bonds. The method according to claim 9, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

16. The aforementioned cyclic lipidized peptide is peptide CLP10: 【Transformation 34】 (Here, * =C18DA-γGlu-OEG-OEG-, where the cyclic peptide is cyclized and all residues of the peptide backbone are connected only by peptide bonds. The method according to claim 9, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

17. The aforementioned peptide has the sequence: 【Chemistry 35】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A cyclic peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X 2 If P, then X 3 A method according to any one of claims 1 to 4, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use (where is other than V).

18. The aforementioned cyclic peptide has the following sequence: 【Transformation 36】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) (Here, X 2 If P, then X 3 The method according to claim 17, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the peptide, wherein the peptide comprises (other than V), the peptide comprises 15 or fewer amino acid residues in a ring, is cyclized, and all residues of the peptide skeleton are connected only by peptide bonds.

19. The aforementioned cyclic peptide has the following sequence: 【Chemistry 37】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) (Here, X 2 If P, then X 3 The method according to claim 18, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the peptide, wherein the peptide comprises (other than V), the peptide comprises 15 or fewer amino acid residues in a ring, is cyclized, and all residues of the peptide skeleton are connected only by peptide bonds. 【Request Item 20】 【Table 2】 A method according to any one of claims 17 to 19, wherein the peptide is cyclized and all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use.

21. The aforementioned cyclic peptide is peptide CP7: 【Transformation 38】 (Here, the peptide is cyclized, and all residues of the peptide backbone are connected only by peptide bonds.) The method according to claim 20, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

22. The aforementioned cyclic peptide is peptide CP9: 【Chemistry 39】 (Here, the peptide is cyclized, and all residues of the peptide backbone are connected only by peptide bonds.) The method according to claim 20, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

23. The aforementioned cyclic peptide is peptide CP10: 【Chemistry 40】 (Here, the peptide is cyclized, and all residues of the peptide backbone are connected only by peptide bonds.) The method according to claim 19, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

24. The peptide comprises 10 or fewer amino acid residues in the ring, and has the following sequence: 【Chemistry 41】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, according to any one of claims 1 to 4, comprising a cyclic peptide containing or a conservatively substituted variant of SEQ ID NO:

51.

25. The aforementioned cyclic peptide has the following sequence: 【Chemistry 42】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) The method according to claim 24, comprising, wherein the peptide is cyclized and all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

26. The aforementioned cyclic peptide has the following sequence: 【Chemistry 43】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) The method according to claim 25, comprising, wherein the peptide is cyclized and all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

27. The cyclic peptide, Table 3 A method according to any one of claims 24 to 26, wherein the peptide is cyclized and all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use.

28. The aforementioned peptide has the sequence: 【Chemistry 44】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, according to any one of claims 1 to 4, comprising a lipidized linear peptide containing or a conservatively substituted variant of SEQ ID NO:

51.

29. The aforementioned lipid-containing linear peptide has the following sequence: 【Chemistry 45】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) The method according to claim 28, comprising, wherein the peptide comprises 15 or fewer amino acid residues, and all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

30. The aforementioned lipid-containing linear peptide has the following sequence: 【Chemistry 46】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) The method according to claim 29, comprising, wherein the peptide comprises 15 or fewer amino acid residues, and all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

31. The method according to claim 30, wherein the lipid of the lipidized cyclic peptide is C18DA-γGlu-OEG-OEG-, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

32. The aforementioned lipid-containing linear peptide, Table 4 A method according to any one of claims 28 to 31, wherein selected from, therein, all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

33. The aforementioned peptide has the sequence: 【Chemistry 47】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A linear peptide containing or containing a conservatively substituted variant of SEQ ID NO: 51 (where X 2 If P, then X 3 A method according to any one of claims 1 to 4, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use (where is other than V).

34. The linear peptide has the following sequence: 【Chemistry 48】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) (Here, X 2 If P, then X 3 The method according to claim 33, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use of the peptide, wherein the peptide comprises (other than V), and the peptide comprises 15 or fewer amino acid residues, and all residues of the peptide backbone are connected only by peptide bonds.

35. The linear peptide has the following sequence: 【Chemistry 49】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) (Here, X 2 If P, then X 3 The method according to claim 34, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use of the peptide, wherein the peptide comprises (other than V), and the peptide comprises 15 or fewer amino acid residues, and all residues of the peptide backbone are connected only by peptide bonds.

36. The peptide comprises 10 or fewer amino acid residues in its backbone, and has the following sequence: [Transformation 50] (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use, according to any one of claims 1 to 4, comprising a linear peptide containing or a conservatively substituted variant of SEQ ID NO:

51.

37. The linear peptide has the following sequence: 【Chemistry 51】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) The method according to claim 36, comprising, wherein all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

38. The linear peptide has the following sequence: 【Chemistry 52】 (Here: X 2 These represent P, D, Q, K, and G. X 3 These represent I, L, A, T, V, X 4 (This represents E and A.) The method according to claim 37, comprising, wherein all residues of the peptide skeleton are connected only by peptide bonds, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use.

39. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use according to any one of claims 1 to 38, wherein the disease or disorder of the ear or mastoid process is a vestibular syndrome (e.g., Meniere's disease or vertigo syndrome).

40. A method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use according to any one of claims 1 to 39, wherein the disease or disorder of the ear or mastoid process is a disease or disorder accompanied by hearing loss or hearing impairment.

41. The method according to claim 40, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the hearing loss is sensorineural hearing loss.

42. The method according to claim 40 or 41, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the hearing loss is a result of mitochondrial disease.

43. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use according to any one of claims 40 to 42, wherein the hearing loss is latent hearing loss.

44. The method, peptide for use or a pharmaceutically acceptable salt thereof, pharmaceutical composition for use, or use according to any one of claims 40 to 43, wherein the hearing loss is hearing loss of auditory synaptopathy.

45. A method according to any one of claims 1 to 44, a peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or a use, wherein the administration of the peptide results in improved hearing.

46. The method according to any one of claims 1 to 45, the peptide for use or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for use, or use, wherein the administration of the peptide results in an increase in the number of cochlear ribbon synapses, spiral ganglion neuron fibers, spiral ganglion neuron cells, inner hair cells, and / or outer hair cells.

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