Compounds comprising modified w peptide

Abstract

The present invention relates to compounds comprising a modified W peptide analogue and optionally a conjugated moiety, and further optionally a linking group linking the modified W peptide and the conjugated moiety.

Description

[0001] P7348PC00

[0002] Compounds comprising modified W Peptide

[0003] Technical field

[0004] The present invention relates to compounds comprising a modified W peptide and optionally a conjugated moiety, and further optionally a linking group linking the modified W peptide and the conjugated moiety.

[0005] Background

[0006] Proteins and peptides are widely employed for therapeutic purposes whether in their native forms, variant forms or analogues thereof. Protein therapeutics tend to be specific for their targets, leading to potentially fewer side effects, but often with lower bioavailability, poorer membrane permeability, and metabolic instability, as compared to small molecules. Protein-based drugs are generally referred to as ‘biologies’ and include molecules such as insulin, growth factors, and engineered antibodies

[0007] Peptides represent a class of molecules that have the specificity and potency of larger protein biologies, but are smaller in size and more accessible and cheaper to manufacture using chemical methods, thus potentially combining some of the advantages of proteins with those of small molecules.

[0008] The W peptide is a synthetic hexapeptide with the sequence Trp-Lys-Tyr-Met-Val-[D- Met] (WKYMVm) (SEQ ID NO: 5). The W peptide exerts an anti-inflammatory effect in various inflammatory diseases by enhancing phagocyte chemotaxis and modulating the secretion of inflammatory mediators (Huan Ma et al, Front Pharmacol. 13:986963, 2022).

[0009] The W peptide is an agonist of the human formyl peptide receptor 2 (FPR2) which plays a crucial role in host defence and inflammation, and has been considered as a drug target for chronic inflammatory diseases. Prior studies have established the critical role of the C-terminal D-Met at position 6 of the W peptide for receptor activity and have indicated challenges associated with its substitution (Chen et al, Nature Communications, 11, 1208, 2020). P7348PC00

[0010] Summary

[0011] The present inventors have demonstrated that replacing the C-terminal D-Met at position 6 of the W peptide (SEQ ID NO: 5) with any one of D-Nle, D-Hse(Me) or D- Ser(Me) unexpectedly retain full receptor activity at FPR receptors. The present inventors further developed FPR2-selective compounds comprising modified W peptide and optionally a conjugated moiety (‘M’), and further optionally a linking group (‘L’) linking the modified W peptide and the conjugated moiety.

[0012] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of:

[0013] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0014] XX 1 is Trp, Bta or 1-Nal,

[0015] XX2 is Lys, Lys(Ac) or Arg,

[0016] XX3 is Tyr, Trp or Arg,

[0017] XX4 is Met or Nle,

[0018] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0019] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, in some embodiments with the proviso that when XX6 is Met or D-Met, then: a. XX1 is Bta or 1-Nal, and / or b. XX2 is Lys(Ac) or Arg, and / or c. XX3 is Trp or Arg, and / or d. XX4 is Nle, and / ore. XX5 is Ser, Tyr, Pro(4NH2) or Hyp.

[0020] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of:

[0021] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0022] XX1 is Trp, Bta or 1-Nal, P7348PC00

[0023] XX2 is Lys, Lys(Ac) or Arg,

[0024] XX3 is Tyr, Trp or Arg,

[0025] XX4 is Met or Nle,

[0026] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0027] XX6 is D-Nle, D-Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX5 of the peptide.

[0028] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of:

[0029] XX1-XX2-XX3-Nle-XX5-XX6 (SEQ ID NO: 2) wherein

[0030] XX 1 is Trp, Bta or 1-Nal,

[0031] XX2 is Lys, Lys(Ac) or Arg,

[0032] XX3 is Tyr, Trp or Arg,

[0033] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0034] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 ,XX2, XX3 or XX5 of the peptide.

[0035] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of:

[0036] Trp-Lys-XX3-XX4-XX5-XX6 (SEQ ID NO: 3) wherein

[0037] XX3 is Tyr, Trp or Arg,

[0038] XX4 is Met or Nle,

[0039] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0040] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 to XX5 of the peptide.

[0041] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of: P7348PC00

[0042] Trp-Lys-XX3-Nle-XX5-XX6 (SEQ ID NO: 4) wherein

[0043] XX3 is Tyr, Trp or Arg,

[0044] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0045] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 or XX5 of the peptide.

[0046] In some embodiments, the present disclosure relates to a compound of Formula I: (M)-(P) wherein (P) is a peptide consisting of:

[0047] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0048] XX 1 is Trp, Bta or 1-Nal,

[0049] XX2 is Lys, Lys(Ac) or Arg,

[0050] XX3 is Tyr, Trp or Arg,

[0051] XX4 is Met or Nle,

[0052] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0053] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, and wherein (M) is a conjugated moiety.

[0054] In some embodiments, the present disclosure relates to a compound of Formula II: (M)-(L)-(P) wherein (P) is a peptide consisting of:

[0055] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0056] XX1 is Trp, Bta or 1-Nal,

[0057] XX2 is Lys, Lys(Ac) or Arg,

[0058] XX3 is Tyr, Trp or Arg,

[0059] XX4 is Met or Nle, P7348PC00

[0060] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0061] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, wherein (M) is a conjugated moiety, and

[0062] (L) is a linking group.

[0063] In some embodiments, the present disclosure relates to a pharmaceutical composition comprising a compound according to the present disclosure; a compound or a pharmaceutical according to the present disclosure for use as a medicament; and a compound or a pharmaceutical composition according to the present disclosure for use in the treatment of chronic inflammation.

[0064] Description of Drawings

[0065] Fig. 1 shows bias factor presented as AA(Emax / EC50). Values above the x-axis (>0) indicate a preference for the Ca2+ pathway, and below the x-axis (<0) indicate a preference for the cAMP pathway.

[0066] 1 : Compounds of Formula II: (M)-(L)-(P), wherein (P) is a peptide consisting of: Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10).

[0067] 2: Compounds of Formula II: (M)-(L)-(P), wherein (P) is a peptide consisting of: Trp-XX2-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 50), wherein XX2 is Arg or Lys(Ac).

[0068] 3: Compounds of Formula II: (M)-(L)-(P), wherein (P) is a peptide consisting of: Trp-Lys-XX3-Nle-Val-[D-Nle] (SEQ ID NO: 51), wherein XX3 is Trp or Arg.

[0069] 4: Compounds of Formula II: (M)-(L)-(P), wherein (P) is a peptide consisting of: Trp-Lys-Tyr-Nle-XX5-[D-Nle] (SEQ ID NO: 52), wherein XX5 is Ser, Hyp, Pro(4NH2) or Tyr.

[0070] 5: Compounds of Formula II: (M)-(L)-(P), wherein (P) is a peptide consisting of: Trp-Lys-XX3-Nle-XX5-[D-Nle] (SEQ ID NO: 53), wherein XX3 is Trp or Arg and XX5 is Hyp or Tyr.

[0071] Fig. 2 shows IL-6 concentration determined by ELISA in human whole blood assay.

[0072] A: LPS-induced IL-6 secretion across three donors.

[0073] B: IL-6 secretion across three donors in the absence of LPS stimulation. P7348PC00

[0074] Definitions

[0075] The singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0076] The term "subject" or “individual” for purposes of treatment includes any subject, and preferably is a subject who is in need of treatment of chronic inflammation. The subject is typically an animal, more typically a mammal. Preferably, the mammal is a human.

[0077] A "therapeutically effective amount" refers to an amount of the compound according to the present disclosure that is nontoxic but sufficient in treating, preventing or ameliorating the severity of an ischemic and inflammatory condition.

[0078] A "pharmaceutically acceptable carrier" as used herein is non-toxic or has certain toxic attributes that are not dose limiting to achieve therapeutic advantages to recipients at the dosages and concentrations required and is compatible with other ingredients of the formulation.

[0079] The term "pharmaceutically acceptable excipient," includes vehicles, adjuvants, or diluents or other auxiliary substances, such as those conventional in the art, which are readily available to the public, and which are non-toxic or have acceptable toxicities to recipients at the dosages and concentrations employed, and is compatible with other ingredients of the formulation. For example, pharmaceutically acceptable auxiliary substances include pH adjusting and buffering agents, tonicity adjusting agents, stabilizers, anti-oxidants, preservatives, solubilizes, wetting agents and the like.

[0080] The term "pharmaceutical composition" or "pharmaceutical formulation" is intended to encompass a drug product including the active ingredient(s), pharmaceutically acceptable excipients that make up the carrier, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients. Accordingly, the pharmaceutical compositions of the present disclosure encompass any composition made by admixing the active ingredient, active ingredient dispersion or composite, additional active ingredient(s), and pharmaceutically acceptable excipients. P7348PC00

[0081] Detailed description

[0082] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of :

[0083] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0084] XX 1 is Trp, Bta or 1-Nal,

[0085] XX2 is Lys, Lys(Ac) or Arg,

[0086] XX3 is Tyr, Trp or Arg,

[0087] XX4 is Met or Nle,

[0088] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0089] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide.

[0090] According to the present disclosure it is understood that in the peptide (P), XX1 to XX6 are contiguous or consecutive amino acids of a hexapeptide, where XX1 is an amino acid at ‘position T corresponding to the N-terminal amino acid; XX2 is an amino acid at ‘position 2’, XX3 is an amino acid at ‘position 3’, XX4 is an amino acid at ‘position 4’, XX5 is an amino acid at ‘position 5’, and XX6 is an amino acid at ‘position 6’ corresponding to the C-terminal amino acid of a hexapeptide.

[0091] Reference herein to ‘or a functional variant thereof having 1 amino acid substitution’ is equivalent to ‘or a functional variant thereof having a single amino acid substitution’, i.e. the functional variant having 1 amino acid substitution of the present disclosure has only one or exactly one i.e. a single amino acid substitution.

[0092] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of:

[0093] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0094] XX1 is Trp, Bta or 1-Nal,

[0095] XX2 is Lys, Lys(Ac) or Arg,

[0096] XX3 is Tyr, Trp or Arg, P7348PC00

[0097] XX4 is Met or Nle,

[0098] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0099] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, with the proviso that when XX6 is Met or D-Met, then: a. XX1 is Bta or 1-Nal, and / or b. XX2 is Lys(Ac) or Arg, and / or c. XX3 is Trp or Arg, and / or d. XX4 is Nle, and / or e. XX5 is Ser, Tyr, Pro(4NH2) or Hyp.

[0100] In some embodiments in peptide (P) of the present disclosure, when XX6 is Met or D- Met, then XX1 is Bta or 1-Nal.

[0101] In some embodiments in peptide (P) of the present disclosure, when XX6 is Met or D- Met, then XX2 is Lys(Ac) or Arg.

[0102] In some embodiments in peptide (P) of the present disclosure, when XX6 is Met or D- Met, then XX3 is Trp or Arg.

[0103] In some embodiments in peptide (P) of the present disclosure, when XX6 is Met or D- Met, then XX4 is Nle.

[0104] In some embodiments in peptide (P) of the present disclosure, when XX6 is Met or D- Met, then XX5 is Ser, Tyr, Pro(4NH2) or Hyp.

[0105] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of :

[0106] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0107] XX 1 is Trp, Bta or 1-Nal,

[0108] XX2 is Lys, Lys(Ac) or Arg,

[0109] XX3 is Tyr, Trp or Arg,

[0110] XX4 is Met or Nle,

[0111] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0112] XX6 is D-Nle, D-Hse(Me) or D-Ser(Me), P7348PC00 or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX5 of the peptide.

[0113] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of :

[0114] XX1-XX2-XX3-Nle-XX5-XX6 (SEQ ID NO: 2) wherein

[0115] XX 1 is Trp, Bta or 1-Nal,

[0116] XX2 is Lys, Lys(Ac) or Arg,

[0117] XX3 is Tyr, Trp or Arg,

[0118] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0119] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of the peptide.

[0120] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of :

[0121] XX1-XX2-XX3-Nle-XX5-XX6 (SEQ ID NO: 2) wherein

[0122] XX1 is Trp, Bta or 1-Nal,

[0123] XX2 is Lys, Lys(Ac) or Arg,

[0124] XX3 is Tyr, Trp or Arg,

[0125] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0126] XX6 is D-Nle, D-Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of the peptide.

[0127] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of :

[0128] Trp-Lys-XX3-XX4-XX5-XX6 (SEQ ID NO: 3) wherein

[0129] XX3 is Tyr, Trp or Arg,

[0130] XX4 is Met or Nle,

[0131] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and P7348PC00

[0132] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 to XX5 of the peptide.

[0133] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of :

[0134] Trp-Lys-XX3-XX4-XX5-XX6 (SEQ ID NO: 3) wherein

[0135] XX3 is Tyr, Trp or Arg,

[0136] XX4 is Met or Nle,

[0137] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0138] XX6 is D-Nle, D-Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 to XX5 of the peptide.

[0139] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of:

[0140] Trp-Lys-XX3-Nle-XX5-XX6 (SEQ ID NO: 4) wherein

[0141] XX3 is Tyr, Trp or Arg,

[0142] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0143] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 or XX5 of the peptide.

[0144] In some embodiments, the present disclosure relates to a compound comprising a peptide (P) consisting of:

[0145] Trp-Lys-XX3-Nle-XX5-XX6 (SEQ ID NO: 4) wherein

[0146] XX3 is Tyr, Trp or Arg,

[0147] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0148] XX6 is D-Nle, D-Hse(Me) or D-Ser(Me), P7348PC00 or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 or XX5 of the peptide.

[0149] In some embodiments a compound of the present disclosure comprises a peptide (P) according to the present disclosure and a conjugated moiety (M), optionally comprising a linking group (L) linking the peptide (P) and the conjugated moiety (M).

[0150] In some embodiments, the present disclosure relates to a compound of Formula I: (M)-(P) wherein (P) is a peptide consisting of:

[0151] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0152] XX 1 is Trp, Bta or 1-Nal,

[0153] XX2 is Lys, Lys(Ac) or Arg,

[0154] XX3 is Tyr, Trp or Arg,

[0155] XX4 is Met or Nle,

[0156] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0157] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, and M is a conjugated moiety.

[0158] In some embodiments, the present disclosure relates to a compound of Formula I: (M)-(P) wherein (P) is a peptide consisting of:

[0159] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0160] XX1 is Trp, Bta or 1-Nal,

[0161] XX2 is Lys, Lys(Ac) or Arg,

[0162] XX3 is Tyr, Trp or Arg,

[0163] XX4 is Met or Nle,

[0164] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and P7348PC00

[0165] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, with the proviso that when XX6 is Met or D-Met, then: a. XX1 is Bta or 1-Nal, and / or b. XX2 is Lys(Ac) or Arg, and / or c. XX3 is Trp or Arg, and / or d. d. XX4 is Nle, and / or e. XX5 is Ser, Tyr, Pro(4NH2) or Hyp; and M is a conjugated moiety.

[0166] In some embodiments, the present disclosure relates to a compound of Formula I: (M)-(P) wherein (P) is a peptide consisting of:

[0167] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0168] XX 1 is Trp, Bta or 1-Nal,

[0169] XX2 is Lys, Lys(Ac) or Arg,

[0170] XX3 is Tyr, Trp or Arg,

[0171] XX4 is Met or Nle,

[0172] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0173] XX6 is D-Nle, D-Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, and M is a conjugated moiety.

[0174] In some embodiments, the peptide (P) consists of:

[0175] XX1-XX2-XX3-Nle-XX5-XX6 (SEQ ID NO: 2) wherein

[0176] XX1 is Trp, Bta or 1-Nal,

[0177] XX2 is Lys, Lys(Ac) or Arg,

[0178] XX3 is Tyr, Trp or Arg,

[0179] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and P7348PC00

[0180] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of the peptide.

[0181] In some embodiments, the peptide (P) consists of::

[0182] Trp-Lys-XX3-XX4-XX5-XX6 (SEQ ID NO: 3) wherein

[0183] XX3 is Tyr, Trp or Arg,

[0184] XX4 is Met or Nle,

[0185] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0186] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 to XX5 of the peptide.

[0187] In some embodiments, the peptide (P) consists of::

[0188] Trp-Lys-XX3-Nle-XX5-XX6 (SEQ ID NO: 4) wherein

[0189] XX3 is Tyr, Trp or Arg,

[0190] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0191] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 or XX5 of the peptide.

[0192] In some embodiments, the present disclosure relates to a compound of Formula II:

[0193] (M)-(L)-(P) wherein (P) is a peptide consisting of:

[0194] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0195] XX 1 is Trp, Bta or 1-Nal,

[0196] XX2 is Lys, Lys(Ac) or Arg,

[0197] XX3 is Tyr, Trp or Arg,

[0198] XX4 is Met or Nle, P7348PC00

[0199] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0200] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide,

[0201] (M) is a conjugated moiety, and

[0202] (L) is a linking group.

[0203] In some embodiments, the present disclosure relates to a compound of Formula II:

[0204] (M)-(L)-(P) wherein (P) is a peptide consisting of:

[0205] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0206] XX 1 is Trp, Bta or 1-Nal,

[0207] XX2 is Lys, Lys(Ac) or Arg,

[0208] XX3 is Tyr, Trp or Arg,

[0209] XX4 is Met or Nle,

[0210] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0211] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, with the proviso that when XX6 is Met or D-Met, then: a. XX1 is Bta or 1-Nal, and / or b. XX2 is Lys(Ac) or Arg, and / or c. XX3 is Trp or Arg, and / or d. XX4 is Nle, and / or e. XX5 is Ser, Tyr, Pro(4NH2) or Hyp;

[0212] (M) is a conjugated moiety, and

[0213] (L) is a linking group.

[0214] In some embodiments, the present disclosure relates to a compound of Formula II:

[0215] (M)-(L)-(P) P7348PC00 wherein (P) is a peptide consisting of:

[0216] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0217] XX 1 is Trp, Bta or 1-Nal,

[0218] XX2 is Lys, Lys(Ac) or Arg,

[0219] XX3 is Tyr, Trp or Arg,

[0220] XX4 is Met or Nle,

[0221] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0222] XX6 is D-Nle, D-Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide,

[0223] (M) is a conjugated moiety, and

[0224] (L) is a linking group.

[0225] In some embodiments, the peptide (P) consists of:

[0226] XX1-XX2-XX3-Nle-XX5-XX6 (SEQ ID NO: 2) wherein

[0227] XX1 is Trp, Bta or 1-Nal,

[0228] XX2 is Lys, Lys(Ac) or Arg,

[0229] XX3 is Tyr, Trp or Arg,

[0230] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0231] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of the peptide.

[0232] In some embodiments, the peptide (P) consists of:

[0233] Trp-Lys-XX3-XX4-XX5-XX6 (SEQ ID NO: 3) wherein

[0234] XX3 is Tyr, Trp or Arg,

[0235] XX4 is Met or Nle,

[0236] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0237] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), P7348PC00 or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 to XX5 of the peptide.

[0238] In some embodiments, the peptide (P) consists of:

[0239] Trp-Lys-XX3-Nle-XX5-XX6 (SEQ ID NO: 4) wherein

[0240] XX3 is Tyr, Trp or Arg,

[0241] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0242] XX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 or XX5 of the peptide.

[0243] In some embodiments it follows that in peptide (P) when XX6 is Met or D-Met, then: a. XX1 is Bta or 1-Nal, and / or b. XX2 is Lys(Ac) or Arg, and / or c. XX3 is T rp or Arg, and / or d. XX5 is Ser, Tyr, Pro(4NH2) or Hyp.

[0244] In some embodiments in peptide (P) of the present disclosure, when XX6 is Met or D- Met, then XX1 is Bta or 1-Nal.

[0245] In some embodiments in peptide (P) of the present disclosure, when XX6 is Met or D- Met, then XX2 is Lys(Ac) or Arg.

[0246] In some embodiments in peptide (P) of the present disclosure, when XX6 is Met or D- Met, then XX3 is Trp or Arg.

[0247] In some embodiments in peptide (P) of the present disclosure, when XX6 is Met or D- Met, then XX4 is Nle.

[0248] In some embodiments in peptide (P) of the present disclosure, when XX6 is Met or D- Met, then XX5 is Ser, Tyr, Pro(4NH2) or Hyp.

[0249] In some embodiments, the peptide (P) of the present disclosure consists of: a. Trp-XX2-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 50), wherein XX2 is Arg or Lys(Ac), b. Trp-Lys-XX3-Nle-Val-[D-Nle] (SEQ ID NO: 51), wherein XX3 is Trp or Arg, P7348PC00 c. Trp-Lys-Tyr-Nle-XX5-[D-Nle] (SEQ ID NO: 52), wherein XX5 is Ser, Hyp, Pro(4NH2) or Tyr, or d. Trp-Lys-XX3-Nle-XX5-[D-Nle] (SEQ ID NO: 53), wherein XX3 is Trp or Arg and XX5 is Hyp or Tyr.

[0250] In some embodiments, the peptide (P) of the present disclosure consists of a peptide selected from any one of SEQ ID NO: 50-53, or a functional variant of any one of SEQ ID NO: 50-53 having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, such as having 1 amino acid substitution in any one of positions XX2, XX3 orXX5 of said peptide.

[0251] A functional variant of a peptide (P) according to the present disclosure means that the variant essentially retains the functionality of the peptide (P) from which it is derived. The functional variant according to the present disclosure may have 1 , 2 or 3 amino acid substitutions, amino acid deletions and / or amino acid insertions compared to the reference peptide.

[0252] In some embodiments, the functional variant of a peptide (P) according to the present disclosure has 1 amino acid substitution in any one of positions XX1 to XX6 of the peptide, such as 1 amino acid substitution in any one of positions XX1 to XX5 of the peptide, such as 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of the peptide, such as 1 amino acid substitution in any one of positions XX3 to XX5 of the peptide, such as 1 amino acid substitution in any one of positions XX3 or XX5 of the peptide. As used herein, having 1 amino acid substitution means having a single amino acid substitution.

[0253] In some embodiments, the functional variant of a peptide (P) according to the present disclosure has a single amino acid substitution in any one of positions XX1 to XX6 of the peptide, such as a single amino acid substitution in any one of positions XX1 to XX5 of the peptide, such as 1 a single amino acid substitution in any one of positions XX1, XX2, XX3 or XX5 of the peptide, such as a single amino acid substitution in any one of positions XX3 to XX5 of the peptide, such as a single amino acid substitution in any one of positions XX3 or XX5 of the peptide. P7348PC00

[0254] In some embodiments, the functional variant of a peptide (P) according to the present disclosure has 1 amino acid deletion in any one of positions XX1 to XX6 of the peptide, such as 1 amino acid deletion in any one of positions XX1 to XX5 of the peptide, such as 1 amino acid deletion in any one of positions XX1 , XX2, XX3 or XX5 of the peptide, such as 1 amino acid deletion in any one of positions XX3 to XX5 of the peptide, such as 1 amino acid deletion in any one of positions XX3 or XX5 of the peptide. As used herein, having 1 amino acid deletion means having a single amino acid deletion.

[0255] In some embodiments, the functional variant of a peptide (P) according to the present disclosure has 1 amino acid insertion in any one of positions XX1 to XX6 of the peptide, such as 1 amino acid insertion in any one of positions XX1 to XX5 of the peptide, such as 1 amino acid insertion in any one of positions XX1 , XX2, XX3 or XX5 of the peptide, such as 1 amino acid insertion in any one of positions XX3 to XX5 of the peptide, such as 1 amino acid insertion in any one of positions XX3 or XX5 of the peptide. As used herein, having 1 amino acid insertion means having a single amino acid insertion.

[0256] The genetic code specifies 20 standard amino acids naturally incorporated into polypeptides (proteinogenic): Ala, Arg, Asn, Asp, Cys, Gin, Glu, Gly, His, lie, Leu, Lys, Met, Phe, Pro, Ser, Tyr, Thr, Trp, Vai, and 2 which are incorporated into proteins by unique synthetic mechanisms: Sec (selenocysteine) and Pyl (pyrrolysine). The naturally occurring amino acids are all L-stereoisomers.

[0257] Aside from the 22 standard or natural amino acids, there are many other non-naturally occurring amino acids (non-proteinogenic or non-standard). They are either not found in proteins, or are not produced directly and in isolation by standard cellular machinery. Non-standard amino acids are usually formed through modifications to standard amino acids, such as post-translational modifications. Examples of unnatural amino acids are Abu, Aib, Nle (Norleucine), D-Nle (D-Norleucine), D-Hse(Me) (O-methyl-D- homoserine), Hyp (trans-4-Hydroxy-L-proline), Bta (3-(3-benzothienyl)-L-alanine), 1-Nal (3-(1-Naphthyl)-L-alanine), [Lys(Ac)] (N-e-acetyl-L-lysine), [Pro(4NH2)] (trans-4-amino- L-proline), yGlu (y-L-glutamic acid), D-Orn (D-ornithine, deguanylated arginine), Nal (beta-2-naphthyl-alanine), D-Nal (beta-2-naphthyl-D-alanine), D-Arg, D-Trp, D-Phe and D-Val. P7348PC00

[0258] In some embodiments, the peptide (P) according to the present disclosure or the functional variant thereof has one or more unnatural amino acids, such as 1, 2 or 3 unnatural amino acids, such as one unnatural amino acid. In some embodiments, the peptide (P) according to the present disclosure or the functional variant thereof has a single unnatural amino acid.

[0259] In some embodiments, the unnatural amino acid is Nle (Norleucine), preferably the L- isomeric form. In some embodiments, the unnatural amino acid is D-Nle (D- Norleucine). In some embodiments, the unnatural amino acid is D-Hse(Me) (O-methyl- D-homoserine). In some embodiments, the unnatural amino acid is Hyp (trans-4- Hydroxy-L-proline). In some embodiments, the unnatural amino acid is Bta (3-(3- benzothienyl)-L-alanine). In some embodiments, the unnatural amino acid is 1-Nal (3- (l-Naphthyl)-L-alanine). In some embodiments, the unnatural amino acid is [Lys(Ac)] (N-e-acetyl-L-lysine). In some embodiments, the unnatural amino acid is [Pro(4NH2)] (trans-4-amino-L-proline). In some embodiments, the unnatural amino acid is D- Ser(Me) (O-methyl-D-serine). In some embodiments, the unnatural amino acid is yGlu (y-L-glutamic acid).

[0260] Any amino acids according to the present disclosure may be in the L- or D- configuration. If nothing is specified, reference to the L-isomeric form is preferably meant. If “D-” is specified, reference to D-isomeric form is meant.

[0261] In some embodiments, XX6 of the peptide (P) of the present disclosure is D-Nle, D- Hse(Me) or D-Ser(Me). In some embodiments, XX6 of the peptide (P) of the present disclosure is D-Nle or D-Hse(Me). In some embodiments, XX6 of the peptide (P) of the present disclosure is D-Nle. In some embodiments, XX6 of the peptide (P) of the present disclosure is D-Hse(Me). In some embodiments, XX6 of the peptide (P) of the present disclosure is D-Ser(Me).

[0262] In some embodiments, XX4 of the peptide (P) of the present disclosure is Met or Nle. In some embodiments, XX4 of the peptide is Nle. In some embodiments, XX4 of the peptide is Met. P7348PC00

[0263] In some embodiments, XX6 of the peptide (P) of the present disclosure is D-Nle, D- Hse(Me) or D-Ser(Me) and XX4 of the peptide (P) of the present disclosure is Nle. In some embodiments, XX6 of the peptide (P) of the present disclosure is D-Nle or D- Hse(Me) and XX4 of the peptide is Nle.

[0264] In some embodiments, XX3 of the peptide (P) of the present disclosure is Trp or Arg. In some embodiments, XX3 of the peptide is Trp. In some embodiments, XX3 of the peptide is Arg. In some embodiments, XX3 of the peptide is Tyr.

[0265] In some embodiments, XX5 of the peptide (P) of the present disclosure is Vai, Tyr or Hyp. In some embodiments, XX5 of the peptide is Vai. In some embodiments, XX5 of the peptide is Ser. In some embodiments, XX5 of the peptide is Tyr. In some embodiments, XX5 of the peptide is Pro(4NH2). In some embodiments, XX5 of the peptide is Hyp.

[0266] In some embodiments, XX1 of the peptide is Trp, Bta or 1-Nal. In some embodiments, XX1 of the peptide is Trp. In some embodiments, XX1 of the peptide is Bta. In some embodiments, XX1 of the peptide is 1-Nal.

[0267] In some embodiments, the compound of the present disclosure comprises or consists of a peptide (P) selected from: a. Bta-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 6) b. Trp-Lys-Tyr-Met-Val-[D-Nle] (SEQ ID NO: 7), c. Trp-Lys-Tyr-Met-Val-[D-Hse(Me)] (SEQ ID NO: 8), d. Trp-Lys-Tyr-Met-Val-[D-Ser(Me)] (SEQ ID NO: 9), e. Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10), f. [1-Nal]-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 11), g. Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO: 37), h. Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 38), i. Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 39), j. Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 40), k. Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 41), l. Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 42), m. Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 43), n. Trp-Lys-Tyr-Nle-[Pro(4NH2)][D-Nle] (SEQ ID NO: 44), P7348PC00 o. Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 45), p. Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 46), q. Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 47), r. Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 48), and s. Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 49).

[0268] In some embodiments, the compound of the present disclosure comprises or consists of a peptide (P) selected from any one of SEQ ID NO: 6-11 and SEQ ID NO: 37-49, or a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1, XX2, XX3 or XX5 of the peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX3 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 orXX5 of said peptide.

[0269] In some embodiments, the compound comprises or consists of a peptide (P) selected from: a. Trp-Lys-Tyr-Met-Val-[D-Nle] (SEQ ID NO: 7), b. Trp-Lys-Tyr-Met-Val-[D-Hse(Me)] (SEQ ID NO: 8), c. Trp-Lys-Tyr-Met-Val-[D-Ser(Me)] (SEQ ID NO: 9), d. Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10), and e. [1-Nal]-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 11).

[0270] In some embodiments, the peptide (P) of the present disclosure consists of: a. Bta-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 6) b. Trp-Lys-Tyr-Met-Val-[D-Nle] (SEQ ID NO: 7), c. Trp-Lys-Tyr-Met-Val-[D-Hse(Me)] (SEQ ID NO: 8), d. Trp-Lys-Tyr-Met-Val-[D-Ser(Me)] (SEQ ID NO: 9), e. Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10), f. [1-Nal]-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 11), g. Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO: 37), P7348PC00 h. Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 38), i. Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 39), j. Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 40), k. Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 41), l. Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 42), m. Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 43), n. Trp-Lys-Tyr-Nle-[Pro(4NH2)][D-Nle] (SEQ ID NO: 44), o. Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 45), p. Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 46), q. Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 47), r. Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 48), or s. Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 49).

[0271] In some embodiments, the peptide (P) of the present disclosure consists of any one of SEQ ID NO: 6-11 and SEQ ID NO: 37-49, or a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1, XX2, XX3 or XX5 of the peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX3 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 orXX5 of said peptide.

[0272] In some embodiments, the peptide (P) of the present disclosure consists of: a. Trp-Lys-Tyr-Met-Val-[D-Nle] (SEQ ID NO: 7), b. Trp-Lys-Tyr-Met-Val-[D-Hse(Me)] (SEQ ID NO: 8), c. Trp-Lys-Tyr-Met-Val-[D-Ser(Me)] (SEQ ID NO: 9), d. Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10), or e. [1-Nal]-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 11).

[0273] In some embodiments, the peptide (P) or compound of the present disclosure further comprises a conjugated moiety (M). In some embodiments, the conjugated moiety is P7348PC00 attached to the N-terminus of the peptide (P), optionally via a linking group (L). In some embodiments, the conjugated moiety (M) is attached to XX1 of the peptide (P), optionally via a linking group (L). In some embodiments, the conjugated moiety (M) is attached to XX1 selected from Trp, Bta and 1-Nal of the peptide (P), optionally via a linking group (L). In some embodiments, the conjugated moiety (M) is attached to the peptide (P) via an amide bond.

[0274] In some embodiments, the conjugated moiety (M) comprises or consists of an acyl group. In some embodiments, the conjugated moiety comprises or consists of an acyl group which originates from a fatty acid or fatty diacid. In some embodiments, the conjugated moiety comprises or consists of an acyl group which originates from a straight-chain fatty acid. In some embodiments, the conjugated moiety comprises or consists of an acyl group which originates from a branched fatty acid. In some embodiments, the conjugated moiety comprises or consists of an acyl group which originates from a fatty acid or fatty diacid with 12 to 22 carbon atoms. In some embodiments, the conjugated moiety comprises or consists of an acyl group which originates from a fatty acid or fatty diacid with 16, 18 or 20 carbon atoms.

[0275] In some embodiments, the conjugated moiety (M) comprises or consists of an acyl group of the formula CH3(CH2)nCO-, wherein n is in an integer of 4 to 24. In some embodiments, the conjugated moiety comprises or consists of one or more acyl groups selected from CH3(CH2)6CO-, CH3(CH2)8CO-, CH3(CH2) CO-, CH3(CH2)I2CO-, CH3(CH2)I4CO-, CH3(CH2)I6CO-, CH3(CH2)I8CO-, CH3(CH2)20CO-, and CH3(CH2)22CO-.

[0276] In some embodiments, the conjugated moiety (M) comprises or consists of an acyl group selected from CH3(CH2)IOCO- (lauryl, C12), CH3(CH2)I2CO- (myristoyl, C14), CH3(CH2)I4CO- (palmitoyl, C16), CH3(CH2)I6CO- (stearyl, C18), CH3(CH2)I8CO- (arachidyl, C20), and CH3(CH2)20CO- (behenyl, C22).

[0277] In some embodiments, the conjugated moiety (M) comprises or consists of an acyl group of the formula COOH(CH2)nCO- (dicarboxylic acid), wherein n is an integer of 4 to 24. In some embodiments, the conjugated moiety comprises or consists of an acyl group selected from COOH(CH2)IOCO- (C12 diacid), COOH(CH2)I2CO- (C14 diacid), COOH(CH2)I4CO- (C16 diacid), COOH(CH2)I5CO- (C17 diacid), COOH(CH2)I6CO- P7348PC00

[0278] (C18 diacid), COOH CH2)I7CO- (C19 diacid), COOH(CH2)I8CO- (C20 diacid), COOH(CH2)I9CO- (C21 diacid), and COOH(CH2)20CO- (C22 diacid).

[0279] In some embodiments, the conjugated moiety comprises or consists of an acyl group selected from COOH(CH2)I4CO-, COOH(CH2)I6CO-, COOH(CH2)I8CO-, and COOH(CH2)2OCO-. In some embodiments, the conjugated moiety molecule comprises or consists of COOH(CH2)i4CO-. In some embodiments, the conjugated moiety comprises or consists of COOH(CH2)ieCO-. In some embodiments, the conjugated moiety comprises or consists of COOH(CH2)I8CO-. In some embodiments, the conjugated moiety comprises or consists of COOH(CH2)2oCO-. In some embodiments, the conjugated moiety comprises or consists of CH3(CH2)i4CO-.

[0280] In some embodiments, the compound of the present disclosure comprise a peptide (P) consisting of: a. Bta-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 6) b. Trp-Lys-Tyr-Met-Val-[D-Nle] (SEQ ID NO: 7), c. Trp-Lys-Tyr-Met-Val-[D-Hse(Me)] (SEQ ID NO: 8), d. Trp-Lys-Tyr-Met-Val-[D-Ser(Me)] (SEQ ID NO: 9), e. Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10), f. [1-Nal]-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 11), g. Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO: 37), h. Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 38), i. Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 39), j. Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 40), k. Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 41), l. Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 42), m. Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 43), n. Trp-Lys-Tyr-Nle-[Pro(4NH2)][D-Nle] (SEQ ID NO: 44), o. Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 45), p. Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 46), q. Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 47), r. Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 48), or s. Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 49), and a conjugated moiety comprising or consisting of an acyl group selected from COOH(CH2)I4CO-, COOH(CH2)I6CO-, COOH(CH2)I8CO-, and COOH(CH2)20CO, P7348PC00 preferably COOH(CH2)ieCO-, and COOH(CH2)ISCO-, more preferred COOH(CH2)I6CO-.

[0281] In some embodiments, the compound of the present disclosure comprise a peptide (P) consisting of any one of any one of SEQ ID NO: 6-11 and SEQ ID NO: 37-49, or a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1, XX2, XX3 or XX5 of the peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX3 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 orXX5 of said peptide; and a conjugated moiety (M) comprising or consisting of an acyl group selected from COOH(CH2)i4CO-, COOH(CH2)I6CO-, COOH(CH2)I8CO-, and COOH(CH2)2oCO, preferably COOH(CH2)i6CO-, and COOH(CH2)i8CO-, more preferred COOH(CH2)I6CO-.

[0282] In some embodiments, the conjugated moiety (M) is COOH(CH2)i6CO- (octadecanedioic acid), referred to as C18 diacid, C18DA or [C18DA], In some embodiments the conjugated moiety (M) is (COOH(CH2)i8CO- (eicosanedioic acid), referred to as C20 diacid, C20DA or [C20DA],

[0283] In some embodiments, the conjugated moiety (M) is CH3(CH2)14CO-, referred to as C16 acid, 016 or

[0016] ,

[0284] In some embodiments, the compound comprising a peptide (P) and a conjugated moiety (M) further comprises a linking group (L). In some embodiments, the conjugated moiety is attached to the N-terminus of the peptide (P) via the linking group (L). In some embodiments, the conjugated moiety (M) is attached to XX1 of the peptide (P) via the linking group. In some embodiments, the conjugated moiety (M) is attached to XX1 selected from Trp, Bta and 1-Nal of the peptide (P) via a linking group (L). In some embodiments, the conjugated moiety (M) and / or the linking group (L) is attached via an amide bond. P7348PC00

[0285] In some embodiments, the linking group (L) comprises or consists of at least one linker compound selected from yGlu (y-L-glutamic acid), PEG8 (3-[2-[2-[2-[2-[2-[2-[2-(2- aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid), Gly and / or OEG (8-amino-3,6-dioxaoctanoic acid).

[0286] In some embodiments, the linking group (L) comprises or consists of at least one, such as one, linker compound selected from yGlu, PEG8, Gly and OEG.

[0287] In some embodiments, the linking group comprises or consists of more than one linker compound individually selected from yGlu, PEG8, Gly and OEG.

[0288] In some embodiments, the linking group comprises or consists of one or more yGlu, such as 1 , 2, 3, 4 or 5 yGlu.

[0289] In some embodiments, the linking group comprises or consists of one or more PEG8, such as 1 , 2, 3, 4 or 5 PEG8.

[0290] In some embodiments, the linking group comprises or consists of one or more Gly, such as 1 , 2, 3, 4 or 5 Gly.

[0291] In some embodiments, the linking group comprises or consists of one or more OEG, such as 1 , 2, 3, 4 or 5 OEG.

[0292] In some embodiments, the linking group (L) of the present disclosure comprises or consists of: a. yGlu-Gly-Gly, b. [PEG8]-Gly-Gly, c. yGlu-[PEG8]-Gly-Gly, d. yGlu-[OEG]-[OEG], e. yGlu-[OEG]-[OEG]-Gly-Gly, or f. yGlu-[OEG]-[OEG]-[OEG]-[OEG]-Gly-Gly.

[0293] In some embodiments, the compound (M)-(L)-(P) of the present disclosure comprises or consists of: a. [C18DA]-yGlu-[PEG8]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 19), b. [C18DA]-yGlu-[OEG][OEG][OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D- Nle] (SEQ ID NO: 20), P7348PC00 c. [C18DA]-yGlu-[OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 21), d. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 22), e. [C18DA]-yGlu-[OEG][OEG]-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO:

[0294] 23), f. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO:

[0295] 24), g. [C18DA]-yGlu-Gly-Gly-Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 25), h. [C18DA]-yGlu-Gly-Gly-Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 26), i. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 27), j. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 28), k. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 29), l. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 30), m. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-[Pro(4NH2)][D-Nle] (SEQ ID NO: 31), n. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 32), o. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 33), p. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 34), q. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 35), or r. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 36).

[0296] In some embodiments, the compound (M)-(L)-(P) of the present disclosure comprises or consists of a compound selected from any one of SEQ ID NO: 19-36, or a functional variant of any one of SEQ ID NO: 19-36 having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide (P), such as a functional variant of any one of SEQ ID NO: 19-36 having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide (P), such as a functional variant of any one of SEQ ID NO: 19-36 having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of said peptide (P), such as a functional variant of any one of SEQ ID NO: 19-36 having 1 amino acid substitution in any one of positions XX3 to XX5 of said peptide (P), such as a functional variant of any one of SEQ ID NO: 19-36 having 1 amino acid substitution in any one of positions XX1 or XX5 of said peptide (P). P7348PC00

[0297] In some embodiments, the compound (M)-(L)-(P) of the present disclosure comprises or consists of: a. [C18DA]-yGlu-[PEG8]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 19), b. [C18DA]-yGlu-[OEG][OEG][OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D- Nle] (SEQ ID NO: 20), c. [C18DA]-yGlu-[OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 21), d. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 22), e. [C18DA]-yGlu-[OEG][OEG]-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO:

[0298] 23), or f. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO:

[0299] 24).

[0300] In some embodiments, the compound of the present disclosure binds one or more of Formyl Peptide Receptor 1 (FPR1) and Formyl Peptide Receptor 2 (FPR2). In some embodiments, the compound activates one or more of Formyl Peptide Receptor 1 (FPR1) and Formyl Peptide Receptor 2 (FPR2). In some embodiments, the compound has different affinities, potencies and / or receptor activation efficacies for FPR1 and FPR2.

[0301] The term “agonist” in the present context refers to a peptide or compound as defined herein, capable of binding to and / or activating, or in some embodiments, capable of binding to at least some extent and / or activating a receptor, or in some embodiments, activating a receptor to at least some extent. For example, a FPR2 agonist is thus capable of binding to and / or activating the FPR2.

[0302] An agonist may be an agonist of several different types of receptors, and thus capable of binding and / or activating several different types of receptors. The agonist can also be a selective agonist which only binds and activates one type of receptor.

[0303] Compounds and peptides, including functional variants thereof, according to the present disclosure are in one embodiment capable of binding and activating to some extent one or several formyl peptide receptors and can have different binding affinities, potencies and / or different receptor activation efficacy for different receptors. Affinity P7348PC00 refers to the number and size of intermolecular forces between a peptide ligand and its receptor, and residence time of the ligand at its receptor binding site. Potency refers to the concentration of a drug or peptide required to elicit a specific effect. Receptor activation efficacy refers to the ability of the peptide ligand to produce a biological response upon binding to the target receptor and the quantitative magnitude of this response. In some embodiments, such differences in affinity, potency and receptor activation efficacy are determined by receptor binding / activation studies which are conventional in the art, for instance by generating ECso and Emax values for stimulation of ligand binding or cellular pathways in cells expressing one or several types of receptors as mentioned herein, or on tissues expressing the different types of receptors. High affinity means that a lower concentration of a ligand is needed to obtain a binding of 50% of the receptors compared to ligand peptides which have lower affinity. High receptor potency means that a lower concentration of the peptide is needed to obtain a 50% receptor activation response (low ECso value), compared to peptides which have lower potency (higher ECso value). Receptor potency might also be referred to as “potency”. Lower than 100% Emax values indicate that the ligand is a partial agonist, meaning it cannot elicit the full biological response of the receptor, even when all receptors are occupied. This contrasts with a full agonist, which reaches 100% Emax and produces the maximum possible response.

[0304] In one embodiment, the compound or the peptide, including functional variants thereof, according to the present disclosure, have different affinities, potencies and / or receptor activation efficacies for FPR1 and FPR2.

[0305] In a particular embodiment, the compound or the peptide, including functional variants thereof, according to the present disclosure, has binding affinity, efficacy and / or potency for the Formyl Peptide Receptor 2 (FPR2). In one particular embodiment, the compound or the peptide, including functional variants thereof, according to the present disclosure, is capable of binding to and activating FPR2. In a further embodiment the compound or the peptide, including functional variants thereof, is a full agonist of FPR2.

[0306] In some embodiments, the compound of the present disclosure binds FPR2. In some embodiments, the compound of the present disclosure activates FPR2. In some embodiments, the compound of the present disclosure is capable of binding to and / or P7348PC00 activating FPR2. In some embodiments, the compound of the present disclosure has binding affinity, efficacy and / or potency for FPR2. In some embodiments, the efficacy and / or potency for FPR2 is measured as FPR2 (Ca2+) ECso and / or FPR2 (cAMP) ECso.

[0307] In some embodiments, the compound of the present disclosure has a FPR2 (Ca2+) ECso of 0.001 to 3000 nM, such as 0.01 to 2000 nM, such as 0.1 to 1000 nM, such as 0.1 to 100 nM, such as 0.1 to 50 nM.

[0308] In some embodiments, the compound of the present disclosure has a FPR2 (Ca2+) ECso of 0.1 to 20 nM , such as 0.1 to 15 nM , such as 0.1 to 14 nM , such as 0.1 to 13 nM, such as 0.1 to 12 nM, such as 0.1 to 11 nM, such as 0.1 to 10 nM, such as 0.1 to 9 nM, such as 0.1 to 8 nM, such as 0.1 to 7 nM, such as 0.1 to 6 nM, such as 0.1 to 5 nM, such as 0.1 to 4 nM, such as 0.1 to 3 nM, such as 0.1 to 2 nM, such as 0.1 to 1 nM, such as 0.1 to 0.5 nM.

[0309] In some embodiments, the compound of the present disclosure has a FPR2 (Ca2+) ECso of 0.2 to 15 nM, such as 0.5 to 15 nM, such as 1 to 15 nM, such as 2 to 15 nM, such as 3 to 15 nM, such as 4 to 15 nM, such as 5 to 15 nM, such as 6 to 15 nM, such as 7 to 15 nM, such as 8 to 15 nM, such as 9 to 15 nM, such as 10 to 15 nM, such as 11 to 15 nM, such as 12 to 15 nM, such as 13 to 15 nM, such as 14 to 15 nM.

[0310] In some embodiments, the compound of the present disclosure has a FPR2 (Ca2+) ECso of 1 to 10 nM, such as 2 to 9 nM, such as 3 to 8 nM, such as 4 to 7 nM, such as 4 to 6 nM, such as 5 to 6 nM.

[0311] In some embodiments, the compound of the present disclosure has a FPR2 (Ca2+) ECso of 1 to 5 nM, such as 1 to 4 nM, such as 1 to 3 nM, such as 2 to 3 nM.

[0312] In some embodiments, the compound of the present disclosure has a FPR2 (Ca2+) ECso of 0.005 to 1 nM, such as 0.01 to 1 nM, such as 0.015 to 1 nM, such as 0.02 to 1 nM, such as 0.025 to 1 nM, such as 0.03 to 1 nM, such as 0.035 to 1 nM, such as 0.04 to 1 nM, such as 0.045 to 1 nM, such as 0.05 to 1 nM, such as 0.055 to 1 nM, such as 0.06 to 1 nM, such as 0.065 to 1 nM, such as 0.07 to 1 nM, such as 0.075 to 1 nM, such as 0.08 to 1 nM, such as 0.085 to 1 nM, such as 0.09 to 1 nM, such as 0.095 to 1 nM.

[0313] In some embodiments, the compound of the present disclosure has a FPR2 (cAMP) ECso of 0.005 to 1 nM, such as 0.01 to 1 nM, such as 0.015 to 1 nM, such as 0.02 to 1 nM, such as 0.025 to 1 nM, such as 0.03 to 1 nM, such as 0.035 to 1 nM, such as 0.04 to 1 nM, such as 0.045 to 1 nM, such as 0.05 to 1 nM, such as 0.055 to 1 nM, such as 0.06 to 1 nM, such as 0.065 to 1 nM, such as 0.07 to 1 nM, such as 0.075 to 1 nM, P7348PC00 such as 0.08 to 1 nM, such as 0.085 to 1 nM, such as 0.09 to 1 nM, such as 0.095 to 1 nM.

[0314] In some embodiments, the compound of the present disclosure has a FPR2 (cAMP) ECso of 1 to 20 nM, such as 1 to 15 nM, such as 1 to 14 nM, such as 1 to 13 nM, such as 1 to 12 nM, such as 1 to 10 nM, such as 1 to 9 nM, such as 1 to 8 nM, such as 1 to 7 nM. such as 1 to 6 nM, such as 1 to 5 nM, such as 1 to 4 nM, such as 1 to 3 nM, such as 1 to 2 nM.

[0315] In some embodiments, the compound of the present disclosure is FPR2 selective. In some embodiments, the compound of the present disclosure has higher selectivity for FPR2 than FPR1.

[0316] In some embodiments, the compound of the present disclosure has at least 2 fold higher selectivity for FPR2 than for FPR1 , such as at least 3 fold, such as at least 4 fold, such as at least 5 fold, such as at least 6 fold, such as at least 7 fold, such as at least 8 fold, such as at least 9 fold, such as at least 10 fold, such as at least 15 fold, such as at least 20 fold, such as at least 25 fold, such as at least 30 fold, such as at least 40 fold, such as at least 50 fold, such as at least 60 fold, such as at least 70 fold, such as at least 80 fold, such as at least 90 fold, such as at least 100 fold higher selectivity for FPR2 than for FPR1.

[0317] In some embodiments, the compound of the present disclosure has more than 100 fold higher selectivity for FPR2 than for FPR1 , such as more than 200 fold, such as more than 300 fold, such as more than 400 fold, such as more than 500 fold, such as more than 600 fold, such as more than 700 fold, such as more than 800 fold, such as more than 900 fold, such as more than 1000 fold, such as more than 1100 fold, such as more than 1200 fold, such as more than 1300 fold, such as more than 1400 fold, such as more than 1500 fold, such as more than 1600 fold, such as more than 1700 fold, such as more than 1800 fold, such as more than 1900 fold, such as more than 2000 fold higher selectivity for FPR2 than for FPR1.

[0318] In some embodiments, the compound of the present disclosure has 400 to 500 fold higher selectivity for FPR2 than for FPR1 , such as 410 to 490, such as 420 to 480, such as 430 to 480, such as 430 to 470, such as 430 to 460, such as 430 to 450, such as 435 to 450, such as 435 to 445 fold higher selectivity for FPR2 than for FPR1.

[0319] In some embodiments, the compound of the present disclosure has 10 to 500 fold higher selectivity for FPR2 than for FPR1 , such as 10 to 400 fold, such as 10 to 300 P7348PC00 fold, such as 10 to 250 fold, such as 10 to 200 fold, such as 10 to 150 fold, such as 10 to 100 fold, such as 10 to 90 fold, such as 10 to 80 fold, such as 10 to 70 fold, such as 10 to 60 fold, such as 10 to 50 fold, such as 10 to 40 fold, such as 10 to 30 fold, such as 10 to 20 fold higher selectivity for FPR2 than for FPR1.

[0320] In some embodiments, the compound of the present disclosure has 10 to 250 fold higher selectivity for FPR2 than for FPR1 , such as 10 to 230 fold, such as 10 to 200 fold, such as 10 to 150 fold, such as 10 to 100 fold, such as 10 to 90 fold, such as 10 to 80 fold, such as 10 to 70 fold, such as 10 to 60 fold, such as 10 to 50 fold, such as 10 to 40 fold, such as 10 to 30 fold, such as 10 to 20 fold higher selectivity for FPR2 than for FPR1.

[0321] In some embodiments, the compound of the present disclosure has 50 to 150 fold higher selectivity for FPR2 than for FPR1 , such as 60 to 140 fold, such as 70 to 130 fold, such as 80 to 120 fold, such as 90 to 120 fold, such as 100 to 120 fold, such as 110 to 120 fold, such as 110 to 115 fold higher selectivity for FPR2 than for FPR1.

[0322] In some embodiments, the compound of the present disclosure has 10 to 50 fold higher selectivity for FPR2 than for FPR1 , such as 11 to 45 fold, such as 12 to 40 fold, such as 13 to 35 fold, such as 14 to 30 fold, such as 15 to 35 fold, such as 16 to 20 fold higher selectivity for FPR2 than for FPR1.

[0323] In some embodiments, the compound of the present disclosure has 1 to 40 fold higher selectivity for FPR2 than for FPR1 , such as 1 to 39 fold, such as 2 to 40 fold, such as 3 to 40 fold, such as 4 to 40 fold, such as 4 to 35 fold, such as 4 to 30 fold, such as 4 to 40 fold, such as 5 to 40 fold, such as 5 to 35 fold, such as 5 to 30 fold, such as 5 to 25 fold, such as 10 to 20 fold, such as 11 to 21 fold, such as 11 to 19 fold higher selectivity for FPR2 than for FPR1.

[0324] In some embodiments, the compound of the present disclosure has 1 to 20 fold higher selectivity for FPR2 than for FPR1 , such as 1 to 19 fold, such as 1 to 18 fold, such as 1 to 17 fold, such as 1 to 16 fold, such as 1 to 15 fold, such as 1 to 14 fold, such as 1 to 13 fold, such as 1 to 12 fold, such as 1 to 11 fold, such as 1 to 10 fold, such as 1 to 9 fold, such as 1 to 8 fold, such as 1 to 7 fold, such as 1 to 6 fold, such as 1 to 5 fold, such as 1 to 4 fold, such as 1 to 3 fold, such as 1 to 2 fold higher selectivity for FPR2 than for FPR1.

[0325] In some embodiments, the higher selectivity for FPR2 than for FPR1 is measured as binding affinity, efficacy and / or potency for FPR2 compared to binding affinity, efficacy and / or potency for FPR1. In some embodiments, the higher selectivity for FPR2 than P7348PC00 for FPR1 is measured as potency for FPR2 compared to potency for FPR1. In some embodiments, the higher selectivity for FPR2 than for FPR1 is measured as FPR2 (Ca2+) ECso and / or FPR2 (cAMP) ECso compared to FPR1 (Ca2+) ECso and / or FPR1 (cAMP) ECso. In some embodiments, the higher selectivity for FPR2 than for FPR1 is measured as FPR2 (Ca2+) ECso compared to FPR1 (Ca2+) ECso.

[0326] In some embodiments, the compound of the present disclosure preferentially activates the Ca2+ pathway. In some embodiments, the compound of the present disclosure preferentially activates the cAMP pathway.

[0327] In some embodiments, the compound of the present disclosure has a Ca2+ / cAMP bias factor of -3 to +1 , such as -2.5 to +0.5, such as -2.5 to 0, such as -2. to 0, such as -1 .5 to -0.5. In some embodiments, the compound of the present disclosure has a Ca2+ / cAMP bias factor of -3 to 0, such as -2.5 to 0, such as -2.5 to -0.5, such as -2.5 to -1. In some embodiments, the compound of the present disclosure has a Ca2+ / cAMP bias factor of 0 to 1 , such as 0 to 0.8, such as 0 to 0.5, such as 0 to 0.3. In some embodiments, the Ca2+ / cAMP bias factor is calculated as Alog(Emax / EC50) Ca2+ pathway - Alog(Emax / EC50) cAMP pathway.

[0328] In some embodiments, the present disclosure relates to a pharmaceutical composition comprising a compound according to the present disclosure. In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient, such as a carrier, an adjuvant and / or a diluent. The pharmaceutical compositions and / or compounds according to the disclosure may be formulated with pharmaceutically acceptable carriers or diluents as well as any other known adjuvants and excipients in accordance with conventional techniques, such as those disclosed in Remington: The Science and Practice of Pharmacy, 20thEdition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 2000.

[0329] Suitable pharmaceutical carriers include inert solid diluents or fillers, sterile aqueous solutions and various organic solvents. Examples of solid carriers are lactose, terra alba, sucrose, cyclodextrin, talc, gelatine, agar, pectin, acacia, magnesium stearate, stearic acid and lower alkyl ethers of cellulose. Examples of liquid carriers are syrup, peanut oil, olive oil, phospholipids, fatty acids, fatty acid amines, polyoxyethylene and water. Moreover, the carrier or diluent may include any sustained release material P7348PC00 known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The pharmaceutical compositions formed by combining the compounds according to the present disclosure and the pharmaceutically acceptable carriers are then readily administered in a variety of dosage forms suitable for the disclosed routes of administration. The formulations may conveniently be presented in unit dosage form by methods known in the art of pharmacy.

[0330] In one embodiment of the present disclosure, a peptide or compound as disclosed herein is generally utilized as a free substance or as a pharmaceutically derivative such as a pharmaceutically acceptable ester or such as a salt thereof. Examples of the latter are: an acid addition salt of a compound having a free base functionality, and a base addition salt of a compound having a free acid functionality. The term “pharmaceutically acceptable salt” refers to a non-toxic salt of a peptide or compound for use according to the present disclosure, which salts are generally prepared by reacting a free base with a suitable organic or inorganic acid, or by reacting an acid with a suitable organic or inorganic base. When a peptide or compound according to the present disclosure contains a free base functionality, such salts are prepared in a conventional manner by treating a solution or suspension of the compound with a chemical equivalent of a pharmaceutically acceptable acid. When a peptide or compound according to the present disclosure contains a free acid functionality, such salts are prepared in a conventional manner by treating a solution or suspension of the compound with a chemical equivalent of a pharmaceutically acceptable base. Physiologically acceptable salts of a peptide or compound with a hydroxy group include the anionic form of the compound in combination with a suitable cation, such as sodium or ammonium ion.

[0331] Other salts which are not pharmaceutically acceptable may be useful in the preparation of peptides or compounds, and they form a further aspect of the disclosure.

[0332] Pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, trifluoroacetate, trichloroacetate, lactate, salicylate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzensulfonate, p-toluenesulfonate and pamoate (i.e., 1 ,1'-methylene-bis-(2-hydroxy-3-naphthoate)) salts. P7348PC00

[0333] In some embodiments, the present disclosure relates to a compound or a pharmaceutical composition according to the present disclosure for use as a medicament. In some embodiments, the present disclosure relates to a compound or a pharmaceutical composition according to the present disclosure for use in the treatment of chronic inflammation.

[0334] P7348PC00

[0335] Examples

[0336] General method of analysis used in Examples 1-5:

[0337] Material:

[0338] All the compounds were synthesized by WuXi AppTec, China. The synthetic hexapeptide Trp-Lys-Tyr-Met-Val-[D-Met] (WKYMVm) (SEQ ID NO: 5), referred to as “W peptide” within the present disclosure, was used as reference ligand in Examples 1- 5. The W peptide is a known FPR1 and FPR2 agonist.

[0339] Compound handling:

[0340] Powders were solubilized in 80:20 DMSO:water at a concentration of 4 mM (master solution). Serial dilutions was performed from master solution in 80:20 DMSO:water to obtain intermediate concentrations 200- or 400-fold higher than the concentrations to be tested, depending on the assay. Each sample was diluted 100-fold in assay specific buffer and dispensed in test plate.

[0341] In vitro testing

[0342] Aequorin assay

[0343] The Aeguorin assay is a luminescence-based intracellular Ca2+ flux assay. In this assay, CHO-K1 cells expressing FPR1 or FPR2 receptors were cultured for 18 hours prior to testing in antibiotic-free media. The cells were then gently detached using PBS- EDTA (5 mM EDTA), collected by centrifugation, and resuspended in an "assay buffer" composed of DMEM / HAM’s F12 with HEPES and 0.1% ovalbumin. The cells were incubated at room temperature for at least 4 hours with Coelenterazine h (Molecular Probes).

[0344] For agonist testing, 50 pl of the cell suspension was added to 50 pl of the test compound or reference ligand, which had been pre-plated in a 96-well plate. The resulting light emission was recorded using the Hamamatsu Functional Drug Screening System 6000 (FDSS 6000).

[0345] To standardize the recorded light emission (determination of the “100% signal”) across plates and different experiments, certain wells contained the reference ligand at a concentration eguivalent to the EC100 obtained during test validation. The agonist P7348PC00 activity of the test compounds was expressed as a percentage of the activity of the reference ligand at its EC100 concentration. cAMP assay

[0346] CHO-K1 cells expressing the human FPR2 receptor were cultured in antibiotic-free media prior to testing. The cells were gently detached using PBS-EDTA (5 mM EDTA), collected by centrifugation, and resuspended in assay buffer (KRH: 5 mM KCI, 1.25 mM MgSO4, 124 mM NaCI, 25 mM HEPES, 13.3 mM Glucose, 1.25 mM KH2PO4, 1.45 mM CaCI2, 0.1% ovalbumin, supplemented with 1 mM IBMX).

[0347] For the agonist test (96-well format), 12 pl of the cell suspension was mixed with 6 pl of the test compound at increasing concentrations and 6 pl of forskolin, followed by a 30- minute incubation at room temperature. After incubation, lysis buffer containing cAMP- d2 and anti-cAMP cryptate detection reagents was added. The plates were then incubated for 1 hour at room temperature, and fluorescence ratios were measured according to the manufacturer's specifications using the CisBio cAMP HTRF Assay Kit. The assay operates on the principle of competition between native cAMP produced by the cells and cAMP labeled with the dye d2 for binding to a cryptate-labeled antibody. The specific signal, corresponding to energy transfer, is inversely proportional to the concentration of cAMP in the sample.

[0348] Bias plot

[0349] Bias plots were created to determine the bias of the agonists towards either Ca2+ or the cAMP pathways relative to the reference ligand (SEQ ID NO: 5) based on the formulae below by calculating relative activities for every agonist in each pathway as described in (Kenakin, 2017, 2019) and used in (Yuliantie et al., 2020). Potencies and efficacies from the cAMP accumulation and Ca2+ assays described above were used.

[0350] First, the logarithm of the efficacy-to-potency ratio, log(Emax / EC50), was calculated for each agonist and pathway. The relative activity was determined by subtracting the log(Emax / EC50) of the reference ligand from that of the test agonist: Alog(Emax / EC50) = log(Emax / EC50)agonist - log(Emax / EC50)reference.

[0351] Next, the bias factor AAIog(Emax / EC50) was calculated by subtracting the cAMP relative activity from that of Ca2+ pathway: Bias factor = AAIog(Emax / EC50) = Alog(Emax / EC50) Ca2+ pathway - Alog(Emax / EC50) cAMP pathway. P7348PC00

[0352] Example 1 : Agonistic properties of modified W peptides analogous at FPR receptors are preserved following position 1, 4 and 6 substitutions

[0353] Given the known chemical instability of methionine (Met) and D-Met, we explored substitutions of W peptide (SEQ ID NO:5) at its amino acid positions 4 and 6. Agonistic properties of the resulting compounds were tested in Aequorin assay, which is a luminescence-based intracellular Ca2+flux assay, in CHO-K1 cells expressing FPR1 or FPR2 receptors.

[0354] Results:

[0355] While prior studies have established the critical role of D-Met at position 6 of the W peptide for receptor activity and have indicated the challenges associated with its substitution (Chen et al 2020), the present findings unexpectedly revealed that replacing D-Met at position 6 of the W peptide with any one of D-Nle, D-Hse(Me) or D- Ser(Me) retained full receptor activity at FPR receptors (Table 1). Remarkably, most of these individual substitutions resulted in compounds with sub-nanomolar potency.

[0356] Furthermore, substitutions at the W peptide position 1 were also well-tolerated, both individually and in combination with alterations at positions 4 and 6 (Cpd 1 and 6). P7348PC00

[0357] Table 1 : Agonistic properties of W peptide analogues substituted at position 1, 4 and / or 6. Aequorin assay was used to determine potency and efficacy of the peptides in cells expressing FPR1 or FPR2 receptors.

[0358] Example 2: Agonistic properties of modified W peptide analogues are preserved or improved when attaching a linking group and fatty diacid derived moiety to the peptide sequence

[0359] The impact of attaching a conjugated moiety in the form of octadecanedioic acid (COOH(CH2)ieCO-, referred to as C18DA) or eicosanedioic acid (COOH(CH2)I8CO-, referred to as C20DA) to the N-terminus with linking groups of varying linker lengths was evaluated using the Ca2+ assay, as detailed above.

[0360] Results:

[0361] The impact of attaching C18DA (COOH(CH2)I6CO-,) or C20DA (COOH(CH2)I8CO-) to the previously described MSR-WP-4 peptide (SEQ ID NO: 12) on receptor potency was investigated. Surprisingly, the results indicate that FPR2 potency is enhanced with the addition of either C18DA (COOH(CH2)I6CO-,) or C20DA (COOH(CH2)I8CO-,) (Cpd 7 and 8) (Table 2).

[0362] Furthermore, attaching a fatty acid moiety via linkers of varying lengths to the modified W peptide analogue consistently retained full FPR receptor activity (Cpd 9-12) (Table 2). Notably, no significant differences in FPR receptor potency were observed with increasing linker length, indicating that linker variation does not adversely affect receptor interaction. P7348PC00

[0363] Table 2: Agonist potency of W peptide analogous comprising a linking group and C18DA (COOH(CH2)i6CO-,) or C20DA (COOH(CH2)i8CO-). Aequorin assay was used to determine potency and efficacy of the peptides in cells expressing FPR1 or FPR2 receptors. MSR-WP-4 comprises C16 (CH3(CH2)i4CO-).

[0364] Example 3: Substitutions at positions 4 and 6 in lipidated compounds enhance selectivity for the FPR2 receptor

[0365] We further explored the effects of combining amino acid substitutions at positions 4 and 6 (Nle and D-Nle, as well as Nle and D-Hse(Me) combinations) with various lipidation and linker strategies. Additionally, we assessed selectivity for the FPR2 receptor by calculating the ratio of potencies (FPR1 / FPR2) determined in the Aequorin assay. P7348PC00

[0366] Results:

[0367] These combinations successfully retained full receptor activity at FPR receptors, with potency maintained in the sub-nanomolar range (cpd 13-18) (Table 3). Interestingly, the introduction of substitutions at positions 4 and 6 in the lipidated compounds significantly enhanced receptor selectivity compared to their non-substituted counterparts (Cpd 7 vs 13; 9 vs 14; 10 vs 15; 11 vs 16; 12 vs 17) (Table 4). Especially, when introducing the combination Nle and Hse(Me) into positions 4 and 6 the selectivity towards FPR2 is increased 39-fold.

[0368] Table 3: Agonist potency of W peptide analogues substituted at position 4 and 6 and comprising a linking group and C18DA (COOH(CH2)i6CO-,). Aequorin assay was used P7348PC00 to determine potency and efficacy of the peptides in cells expressing FPR1 or FPR2 receptors.

[0369] Table 4: FPR2 selectivity of W peptide analogues comprising a linking group and C18DA (COOH(CH2)ieCO-,). Selectivity was calculated as FPR1 / FPR2 potency ratio with potencies determined using the Aequorin assay.

[0370] Example 4: Substitutions at positions 4 and 6 combined with position 2, 3 or 5„ or combined with positions 3 and 5, preserves activity at FPR2 receptor and introduce pathway bias

[0371] Given that FPR receptors signal through both Ca2+ mobilization and the inhibition of cAMP generation via Gi coupling, the compounds' ability to activate the cAMP pathway P7348PC00 was evaluated. To determine the preference for one pathway over the other, a bias factor was calculated based on the relative activities calculated for each compound, as described in the Method section. Results:

[0372] Lipidated compounds with substitutions at amino acid positions 4 and 6 exhibited balanced activation of both cAMP and Ca2+ signalling pathways (Cpd 13-18) (Table 5, Fig. 1). However, when substitutions were introduced at positions 2, 3 or 5, or a combination of 3 and 5, within the Cpd 16 backbone (Cpd 29-40), the compounds activated FPR2 but, unexpectedly, showed a pronounced preference for the cAMP pathway, with a 5- to 159-fold bias (bias factor AAlog [=-0.7 to 2.2]). An exception was observed with compound 39, which features a Trp substitution at position 3 and maintained balanced agonist activity across both pathways. P7348PC00 P7348PC00

[0373] Table 5: Potency of W peptide analogues substituted at positions 4 / 6 and position 2, 3 or 5, or a combination of 3 and 5, and comprising a linking group and C18DA (COOH(CH2)ieCO-,). Potencies at FPR2 receptor were determined using the Aequorin and cAMP assay

[0374] Example 5: Substitutions at positions 4 and 6 combined with position 3 and 5 substitutions drive FPR2 receptor selectivity with unique pharmacological properties

[0375] In vitro testing

[0376] Whole blood assay P7348PC00

[0377] Whole blood assays were conducted under sterile conditions in a laminar flow cabinet. Fresh heparinized peripheral blood was obtained from three healthy human donors and used on the day of collection. All conditions were tested in triplicate for each donor. Heparinized peripheral blood was diluted to yield a final concentration of 50% in the assay wells. The diluted blood was dispensed into 96-well tissue culture plates to a final reaction volume of 120 pL per well. Test compounds were added at final concentrations of 10, 100, or 1000 nM.

[0378] Mixtures were gently homogenized by pipetting and pre-incubated for 15 minutes at 37 °C in a humidified atmosphere of 5% CO2. Thereafter, either lipopolysaccharide (LPS; 0.05 endotoxin units / mL) or vehicle (RPMI 1640) was added to each compound condition. Plates were gently mixed and returned to the incubator for 6 hours.

[0379] Following incubation, plates were centrifuged, and the supernatants collected and stored at -20 °C until biomarker quantification. IL-6 concentrations were determined by ELISA (Mabtech, #3460-1 H-6) according to the manufacturer’s instructions.

[0380] Results:

[0381] When tested in a human whole blood assay, Cpd 30 and Cpd 34, which activate both FPR1 and FPR2 receptors (see Table 6), markedly potentiated LPS-induced IL-6 secretion across all three donors, with IL-6 levels consistently exceeding those observed with LPS stimulation alone (Fig. 2A). The potentiation was concentrationdependent and reproducible across donors.

[0382] In contrast, and unexpectedly, Cpd 38 and Cpd 40, which are selective for FPR2, did not potentiate LPS-induced IL-6 secretion at any tested concentration (10, 100, or 1000 nM) (Fig. 2A). In these cases, IL-6 levels in the presence of LPS remained comparable to LPS alone, indicating the absence of an amplifying effect on the inflammatory response. This lack of IL-6 potentiation suggests a distinct pharmacological profile, consistent with a non-pro-inflammatory mode of action.

[0383] Importantly, none of the peptides alone (in the absence of LPS stimulation) induced measurable IL-6 secretion (Fig. 2B), confirming that the observed effects were dependent on the inflammatory stimulus. P7348PC00

[0384] Table 6: Potency of W peptide analogues substituted at positions 4 / 6 and position 2, 3 or 5, or a combination of 3 and 5, and comprising a linking group and C18DA (COOH(CH2)ieCO-,). Potencies at FPR1 and FPR2 receptor were determined using the Aequorin assay. Selectivity was calculated as FPR1 / FPR2 potency ratio. P7348PC00

[0385] Sequence overview

[0386] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1), wherein

[0387] XX 1 is Trp, Bta or 1-Nal,

[0388] XX2 is Lys, Lys(Ac) or Arg,

[0389] XX3 is Tyr, Trp or Arg,

[0390] XX4 is Met or Nle,

[0391] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0392] XX6 is Met, D-Met, D-Nle, D-Hse(Me) or D-Ser(Me), preferably D-Nle, D-Hse(Me) or D- Ser(Me)

[0393] XX1-XX2-XX3-Nle-XX5-XX6 (SEQ ID NO: 2), wherein

[0394] XX1 is Trp, Bta or 1-Nal,

[0395] XX2 is Lys, Lys(Ac) or Arg,

[0396] XX3 is Tyr, Trp or Arg,

[0397] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0398] XX6 is Met, D-Met, D-Nle, D-Hse(Me) or D-Ser(Me), preferably D-Nle, D-Hse(Me) or D- Ser(Me)

[0399] Trp-Lys-XX3-XX4-XX5-XX6 (SEQ ID NO: 3), wherein

[0400] XX3 is Tyr, Trp or Arg,

[0401] XX4 is Met or Nle,

[0402] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0403] XX6 is Met, D-Met, D-Nle, D-Hse(Me) or D-Ser(Me), preferably D-Nle, D-Hse(Me) or D- Ser(Me)

[0404] Trp-Lys-XX3-Nle-XX5-XX6 (SEQ ID NO: 4), wherein

[0405] XX3 is Tyr, Trp or Arg,

[0406] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and

[0407] XX6 is Met, D-Met, D-Nle, D-Hse(Me) or D-Ser(Me), preferably D-Nle, D-Hse(Me) or D- Ser(Me).

[0408] Trp-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 5)

[0409] Bta-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 6)

[0410] Trp-Lys-Tyr-Met-Val-[D-Nle] (SEQ ID NO: 7)

[0411] Trp-Lys-Tyr-Met-Val-[D-Hse(Me)] (SEQ ID NO: 8) P7348PC00

[0412] Trp-Lys-Tyr-Met-Val-[D-Ser(Me)] (SEQ ID NO: 9) Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10) [1-Nal]-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 11) [C16]-[PEG8]-Gly-Gly-Trp-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 12) [C18DA]-yGlu-[PEG8]-Gly-Gly-Trp-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 13) [C20DA]-yGlu-[PEG8]-Gly-Gly-Trp-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 14) [C18DA]-yGlu-[OEG][OEG][OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 15)

[0413] [C18DA]-yGlu-[OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 16) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 17) [C18DA]-yGlu-[OEG][OEG]-Trp-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 18) [C18DA]-yGlu-[PEG8]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 19) [C18DA]-yGlu-[OEG][OEG][OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 20)

[0414] [C18DA]-yGlu-[OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 21) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 22) [C18DA]-yGlu-[OEG][OEG]-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 23) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO: 24) [C18DA]-yGlu-Gly-Gly-Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 25) [C18DA]-yGlu-Gly-Gly-Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 26) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 27) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 28)

[0415] [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 29) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 30) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-[Pro(4NH2)]-[D-Nle] (SEQ ID NO: 31) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 32) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 33) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 34) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 35) [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 36) Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO: 37)

[0416] Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 38) Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 39) Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 40) Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 41) P7348PC00

[0417] Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 42)

[0418] Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 43)

[0419] Trp-Lys-Tyr-Nle-[Pro(4NH2)][D-Nle] (SEQ ID NO: 44)

[0420] Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 45) Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 46)

[0421] Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 47)

[0422] Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 48)

[0423] Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 49)

[0424] Trp-XX2-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 50), wherein XX2 is Arg or Lys(Ac) Trp-Lys-XX3-Nle-Val-[D-Nle] (SEQ ID NO: 51), wherein XX3 is Trp or Arg

[0425] Trp-Lys-Tyr-Nle-XX5-[D-Nle] (SEQ ID NO: 52), wherein XX5 is Ser, Hyp, Pro(4NH2) or Tyr

[0426] Trp-Lys-XX3-Nle-XX5-[D-Nle] (SEQ ID NO: 53), wherein XX3 is Trp or Arg and XX5 is Hyp or Tyr

[0427] P7348PC00

[0428] Items

[0429] 1. A compound comprising a peptide (P) consisting of :

[0430] XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0431] XX 1 is Trp, Bta or 1-Nal,

[0432] XX2 is Lys, Lys(Ac) or Arg,

[0433] XX3 is Tyr, Trp or Arg,

[0434] XX4 is Met or Nle,

[0435] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and XX6 is D-Nle, D-Hse(Me) or D-Ser(Me).

[0436] 2. The compound according to item 1 of Formula I:

[0437] (M)-(P) wherein (P) is a peptide consisting of: XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0438] XX1 is Trp, Bta or 1-Nal,

[0439] XX2 is Lys, Lys(Ac) or Arg,

[0440] XX3 is Tyr, Trp or Arg,

[0441] XX4 is Met or Nle,

[0442] XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and XX6 is D-Nle, D-Hse(Me) or D-Ser(Me), and (M) is a conjugated moiety.

[0443] 3. The compound according to any one of the preceding items of Formula II:

[0444] (M)-(L)-(P) wherein (P) is a peptide consisting of: XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) wherein

[0445] XX1 is Trp, Bta or 1-Nal,

[0446] XX2 is Lys, Lys(Ac) or Arg,

[0447] XX3 is Tyr, Trp or Arg,

[0448] XX4 is Met or Nle, XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and P7348PC00

[0449] XX6 is D-Nle, D-Hse(Me) or D-Ser(Me),

[0450] (M) is a conjugated moiety, and

[0451] (L) is a linking group.

[0452] 4. The compound according to any one of the preceding items, wherein XX6 of said peptide is D-Nle or D-Hse(Me).

[0453] 5. The compound according to any one of the preceding items, wherein XX4 of said peptide is Nle.

[0454] 6. The compound according to any one of the preceding items, wherein the compound comprises or consists of: a. Bta-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 6) b. Trp-Lys-Tyr-Met-Val-[D-Nle] (SEQ ID NO: 7), c. Trp-Lys-Tyr-Met-Val-[D-Hse(Me)] (SEQ ID NO: 8), d. Trp-Lys-Tyr-Met-Val-[D-Ser(Me)] (SEQ ID NO: 9), e. Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10), f. [1-Nal]-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 11), g. Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO: 37), h. Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 38), i. Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 39), j. Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 40), k. Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 41), l. Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 42), m. Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 43), n. Trp-Lys-Tyr-Nle-[Pro(4NH2)][D-Nle] (SEQ ID NO: 44), o. Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 45), p. Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 46), q. Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 47), r. Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 48), or s. Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 49).

[0455] 7. The compound according to any one of items 2 to 6, wherein the conjugated moiety comprises or consists of an acyl group of the formula CH3(CH2)nCO-, P7348PC00 wherein n is in an integer of 4 to 24 or an acyl group of the formula COOH(CH2)nCO- (dicarboxylic acid), wherein n is an integer of 4 to 24.

[0456] 8. The compound according to any one of items 2 to 7, wherein the conjugated moiety comprises or consists of an acyl group selected from COOH(CH2)i4CO-, COOH(CH2)I6CO-, COOH(CH2)I8CO-, and COOH(CH2)2oCO, preferably COOH(CH2)I6CO- or COOH(CH2)I8CO-, more preferred COOH(CH2)I6CO-.

[0457] 9. The compound according to any one of items 3 to 8, wherein the linking group comprises or consists of one or more yGlu, such as 1 , 2, 3, 4 or 5 yGlu, and / or one or more PEG8, such as 1 , 2, 3, 4 or 5 PEG8, and / or one or more Gly, such as 1 , 2, 3, 4 or 5 Gly, and / or one or more OEG, such as 1 , 2, 3, 4 or 5 OEG.

[0458] 10. The compound according to any one of items 3 to 9, wherein the linking group comprises or consists of: a. yGlu-Gly-Gly, b. [PEG8]-Gly-Gly, c. yGlu-[PEG8]-Gly-Gly, d. yGlu-[OEG]-[OEG], e. yGlu-[OEG]-[OEG]-Gly-Gly, or f. yGlu-[OEG]-[OEG]-[OEG]-[OEG]-Gly-Gly.

[0459] 11 . The compound according to any one of the preceding items, wherein the compound comprises or consists of: a. [C18DA]-yGlu-[PEG8]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 19), b. [C18DA]-yGlu-[OEG][OEG][OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D- Nle] (SEQ ID NO: 20), c. [C18DA]-yGlu-[OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 21), d. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 22), e. [C18DA]-yGlu-[OEG][OEG]-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO:

[0460] 23), f. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO:

[0461] 24), P7348PC00 g. [C18DA]-yGlu-Gly-Gly-Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 25), h. [C18DA]-yGlu-Gly-Gly-Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 26), i. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 27), j. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 28), k. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 29), l. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 30), m. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-[Pro(4NH2)][D-Nle] (SEQ ID NO: 31), n. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 32), o. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 33), p. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 34), q. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 35), or r. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 36).

[0462] 12. The compound according to any one of the preceding items, wherein said compound has at least 2 fold higher selectivity for FPR2 than for FPR1 , such as at least 3 fold, such as at least 4 fold, such as at least 5 fold, such as at least 6 fold, such as at least 7 fold, such as at least 8 fold, such as at least 9 fold, such as at least 10 fold higher selectivity for FPR2 than for FPR1

[0463] 13. A pharmaceutical composition comprising a compound according to any one of the preceding items, optionally further comprising a pharmaceutically acceptable excipient, such as a carrier, an adjuvant and / or a diluent.

[0464] 14. A compound or a pharmaceutical composition according to any one of the preceding items for use as a medicament.

[0465] 15. A compound or a pharmaceutical composition according to any one of the preceding items for use in the treatment of chronic inflammation.

Claims

55P7348PC00Claims1. A compound comprising a peptide (P) consisting of :XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) whereinXX 1 is Trp, Bta or 1-Nal,XX2 is Lys, Lys(Ac) or Arg,XX3 is Tyr, Trp or Arg,XX4 is Met or Nle,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, andXX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, with the proviso that when XX6 is Met or D-Met, then. a. XX1 is Bta or 1-Nal, and / or b. XX2 is Lys(Ac) or Arg, and / or c. XX3 is T rp or Arg, and / or d. XX4 is Nle, and / or e. XX5 is Ser, Tyr, Pro(4NH2) or Hyp.

2. The compound according to claim 1, comprising a peptide (P) consisting of:XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) whereinXX1 is Trp, Bta or 1-Nal,XX2 is Lys, Lys(Ac) or Arg,XX3 is Tyr, Trp or Arg,XX4 is Met or Nle,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and XX6 is D-Nle, D-Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide.56P7348PC003. The compound according to any one of the preceding claims, comprising a peptide (P) consisting of :XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) whereinXX 1 is Trp, Bta or 1-Nal, XX2 is Lys, Lys(Ac) or Arg, XX3 is Tyr, Trp or Arg, XX4 is Met or Nle,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, and XX6 is D-Nle, D-Hse(Me) or D-Ser(Me).

4. A compound comprising a peptide (P) consisting of :XX1-XX2-XX3-Nle-XX5-XX6 (SEQ ID NO: 2) whereinXX1 is Trp, Bta or 1-Nal,XX2 is Lys, Lys(Ac) or Arg,XX3 is Tyr, Trp or Arg,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, andXX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of said peptide.

5. A compound comprising a peptide (P) consisting of :Trp-Lys-XX3-XX4-XX5-XX6 (SEQ ID NO: 3) whereinXX3 is Tyr, Trp or Arg,XX4 is Met or Nle,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, andXX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 to XX5 of said peptide.

6. A compound comprising a peptide (P) consisting of:57P7348PC00Trp-Lys-XX3-Nle-XX5-XX6 (SEQ ID NO: 4) whereinXX3 is Tyr, Trp or Arg,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, andXX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 or XX5 of said peptide.

7. A compound of Formula I:(M)-(P) wherein (P) is a peptide consisting of:XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) whereinXX 1 is Trp, Bta or 1-Nal,XX2 is Lys, Lys(Ac) or Arg,XX3 is Tyr, Trp or Arg,XX4 is Met or Nle,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, andXX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, and (M) is a conjugated moiety.

8. A compound of Formula II:(M)-(L)-(P) wherein (P) is a peptide consisting of:XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) whereinXX1 is Trp, Bta or 1-Nal,XX2 is Lys, Lys(Ac) or Arg,XX3 is Tyr, Trp or Arg,XX4 is Met or Nle,58P7348PC00XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, andXX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide,(M) is a conjugated moiety, and(L) is a linking group.

9. The compound according to any one of claims 7 to 8, wherein in peptide (P) when XX6 is Met or D-Met, then: a. XX1 is Bta or 1-Nal, and / or b. XX2 is Lys(Ac) or Arg, and / or c. XX3 is T rp or Arg, and / or d. XX4 is Nle, and / or e. XX5 is Ser, Tyr, Pro(4NH2) or Hyp.

10. The compound according to any one of claims 7 to 9, wherein (P) is a peptide consisting of:XX1-XX2-XX3-Nle-XX5-XX6 (SEQ ID NO: 2) whereinXX 1 is Trp, Bta or 1-Nal,XX2 is Lys, Lys(Ac) or Arg,XX3 is Tyr, Trp or Arg,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, andXX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of said peptide.

11. The compound according to any one of claims 7 to 10, wherein (P) is a peptide consisting of:Trp-Lys-XX3-XX4-XX5-XX6 (SEQ ID NO: 3) whereinXX3 is Tyr, Trp or Arg,P7348PC00XX4 is Met or Nle,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, andXX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 to XX5 of said peptide.

12. The compound according to any one of claims 7 to 11 , wherein (P) is a peptide consisting of:Trp-Lys-XX3-Nle-XX5-XX6 (SEQ ID NO: 4) whereinXX3 is Tyr, Trp or Arg,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, andXX6 is D-Nle, D-Hse(Me), D-Ser(Me), Met or D-Met, preferably D-Nle, D- Hse(Me) or D-Ser(Me), or a functional variant thereof having 1 amino acid substitution in any one of positions XX3 or XX5 of said peptide.

13. The compound according to any one of claims 7 to 12, wherein (P) is a peptide consisting of:XX1-XX2-XX3-XX4-XX5-XX6 (SEQ ID NO: 1) whereinXX 1 is Trp, Bta or 1-Nal,XX2 is Lys, Lys(Ac) or Arg,XX3 is Tyr, Trp or Arg,XX4 is Met or Nle,XX5 is Vai, Ser, Tyr, Pro(4NH2) or Hyp, andXX6 is D-Nle, D-Hse(Me) or D-Ser(Me).

14. The compound according to any one of the preceding claims, with the proviso that in peptide (P) when XX6 is Met or D-Met, then XX1 is Bta or 1-Nal.

15. The compound according to any one of the preceding claims, with the proviso that in peptide (P) when XX6 is Met or D-Met, then XX2 is Lys(Ac) or Arg,P7348PC0016. The compound according to any one of the preceding claims, with the proviso that in peptide (P) when XX6 is Met or D-Met, then XX3 is Trp or Arg.

17. The compound according to any one of the preceding claims, with the proviso that in peptide (P) when XX6 is Met or D-Met, then XX4 is Nle.

18. The compound according to any one of the preceding claims, with the proviso that in peptide (P) when XX6 is Met or D-Met, then XX5 is Ser, Tyr, Pro(4NH2) or Hyp.

19. The compound according to any one of the preceding claims, wherein the peptide (P) consists of: a. Trp-XX2-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 50), wherein XX2 is Arg or Lys(Ac), b. Trp-Lys-XX3-Nle-Val-[D-Nle] (SEQ ID NO: 51), wherein XX3 is Trp or Arg, c. Trp-Lys-Tyr-Nle-XX5-[D-Nle] (SEQ ID NO: 52), wherein XX5 is Ser, Hyp, Pro(4NH2) or Tyr, d. Trp-Lys-XX3-Nle-XX5-[D-Nle] (SEQ ID NO: 53), wherein XX3 is Trp or Arg and XX5 is Hyp or Tyr, or e. a functional variant of any one of SEQ ID NO: 50-53 having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, preferably having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide.

20. The compound according to any one of the preceding claims, wherein XX6 of said peptide is D-Nle or D-Hse(Me).

21. The compound according to any one of the preceding claims, wherein XX6 of said peptide is D-Nle.

22. The compound according to any one of the preceding claims, wherein XX6 of said peptide is D-Hse(Me).P7348PC0023. The compound according to any one of the preceding claims, wherein XX6 of said peptide is D-Ser(Me).

24. The compound according to any one of the preceding claims, wherein XX4 of said peptide is Met or Nle.

25. The compound according to any one of the preceding claims, wherein XX4 of said peptide is Nle.

26. The compound according to any one of the preceding claims, wherein XX4 of said peptide is Met.

27. The compound according to any one of the preceding claims, wherein XX6 of said peptide is D-Nle, D-Hse(Me) or D-Ser(Me) and XX4 of said peptide is Nle28. The compound according to any one of the preceding claims, wherein XX6 of said peptide is D-Nle or D-Hse(Me) and XX4 of said peptide is Nle.

29. The compound according to any one of the preceding claims, wherein XX3 of said peptide is Trp or Arg.

30. The compound according to any one of the preceding claims, wherein XX3 of said peptide is Trp.

31. The compound according to any one of the preceding claims, wherein XX3 of said peptide is Arg.

32. The compound according to any one of the preceding claims, wherein XX5 of said peptide is Vai, Tyr or Hyp.

33. The compound according to any one of the preceding claims, wherein XX5 of said peptide is Vai.

34. The compound according to any one of the preceding claims, wherein XX5 of said peptide is Ser.62P7348PC0035. The compound according to any one of the preceding claims, wherein XX5 of said peptide is Tyr.

36. The compound according to any one of the preceding claims, wherein XX5 of said peptide is Pro(4NH2).

37. The compound according to any one of the preceding claims, wherein XX5 of said peptide is Hyp.

38. The compound according to any one of the preceding claims, wherein XX1 of said peptide is Trp.

39. The compound according to any one of the preceding claims, wherein XX1 of said peptide is Bta.

40. The compound according to any one of the preceding claims, wherein XX1 of said peptide is 1-Nal.

41. The compound according to any one of the preceding claims, wherein the peptide (P) consists of any one of SEQ ID NO: 6-11 and SEQ ID NO: 37-49.

42. The compound according to any one of the preceding claims, wherein the peptide (P) consists of any one of SEQ ID NO: 6-11 and SEQ ID NO: 37-49, or a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of the peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX3 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 or XX5 of said peptide.63P7348PC0043. The compound according to any one of the preceding claims, wherein the compound comprises or consists of a peptide (P) selected from: a. Bta-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 6) b. Trp-Lys-Tyr-Met-Val-[D-Nle] (SEQ ID NO: 7), c. Trp-Lys-Tyr-Met-Val-[D-Hse(Me)] (SEQ ID NO: 8), d. Trp-Lys-Tyr-Met-Val-[D-Ser(Me)] (SEQ ID NO: 9), e. Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10), f. [1-Nal]-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 11), g. Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO: 37), h. Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 38), i. Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 39), j. Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 40), k. Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 41), l. Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 42), m. Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 43), n. Trp-Lys-Tyr-Nle-[Pro(4NH2)][D-Nle] (SEQ ID NO: 44), o. Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 45), p. Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 46), q. Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 47), r. Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 48), and s. Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 49).

44. The compound according to any one of the preceding claims, wherein the compound comprises or consists of a peptide (P) selected from any one of SEQ ID NO: 6-11 and 37-49, or a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of the peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX3 to XX5 of said peptide,64P7348PC00 such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 or XX5 of said peptide45. The compound according to any one of the preceding claims, wherein the compound comprises or consists of a peptide (P) selected from: a. Trp-Lys-Tyr-Met-Val-[D-Nle] (SEQ ID NO: 7), b. Trp-Lys-Tyr-Met-Val-[D-Hse(Me)] (SEQ ID NO: 8), c. Trp-Lys-Tyr-Met-Val-[D-Ser(Me)] (SEQ ID NO: 9), d. Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10), and e. [1-Nal]-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 11).

46. The compound according to any one of claims 1 to 6, wherein said compound further comprises a conjugated moiety (M).

47. The compound according to any one of the preceding claims, wherein the conjugated moiety is attached to the N-terminus of said peptide (P), optionally via a linking group (L).

48. The compound according to any one of the preceding claims, wherein the conjugated moiety is attached to XX1 of said peptide (P), optionally via a linking group (L).

49. The compound according to any one of the preceding claims, wherein the conjugated moiety is attached via an amide bond.

50. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of an acyl group.

51. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of an acyl group which originates from a fatty acid or fatty diacid.

52. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of an acyl group which originates a straight-chain fatty acid.65P7348PC0053. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of an acyl group which originates from a branched fatty acid.

54. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of an acyl group which originates from a fatty acid or fatty diacid with 12 to 22 carbon atoms.

55. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of an acyl group which originates from a fatty acid or fatty diacid with 16, 18 or 20 carbon atoms.

56. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of an acyl group of the formula CH3(CH2)nCO-, wherein n is in an integer of 4 to 24.

57. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of one or more acyl groups selected from CH3(CH2)6CO-, CH3(CH2)8CO-, CH3(CH2) CO-, CH3(CH2)I2CO-, CH3(CH2)I4CO-, CH3(CH2)I6CO-, CH3(CH2)I8CO-, CH3(CH2)20CO-, and CH3(CH2)22CO-.

58. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of an acyl group selected from CH3(CH2)IOCO- (lauryl, C12), CH3(CH2)I2CO- (myristoyl, C14), CH3(CH2)I4CO- (palmitoyl, C16), CH3(CH2)I6CO- (stearyl, C18), CH3(CH2)I8CO- (arachidyl, C20), andCH3(CH2)20CO- (behenyl, C22).

59. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of an acyl group of the formula COOH(CH2)nCO- (dicarboxylic acid), wherein n is an integer of 4 to 24.

60. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of two acyl groups individually66P7348PC00 selected from COOH(CH2)IOCO- (C12 diacid), COOH(CH2)I2CO- (C14 diacid), COOH(CH2)I4CO- (C16 diacid), COOH(CH2)I5CO- (C17 diacid), COOH(CH2)I6CO- (C18 diacid), COOH CH2)I7CO- (C19 diacid), COOH(CH2)I8CO- (C20 diacid), COOH(CH2)I9CO- (C21 diacid), and COOH(CH2)20CO- (C22 diacid.

61. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of an acyl group selected from COOH(CH2)I4CO-, COOH(CH2)I6CO-, COOH(CH2)I8CO-, and COOH(CH2)20CO-.

62. The compound according to any one of the preceding claims, wherein the conjugated moiety molecule comprises or consists of COOH(CH2)I4CO-.

63. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of COOH(CH2)I8CO-.

64. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of COOH(CH2)I8CO-.

65. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of COOH(CH2)2oCO-.

66. The compound according to any one of the preceding claims, wherein the conjugated moiety comprises or consists of CH8(CH2)I4CO-.

67. The compound according to any one of the preceding claims, wherein the compound comprises a peptide (P) consisting of: a. Bta-Lys-Tyr-Met-Val-[D-Met] (SEQ ID NO: 6) b. Trp-Lys-Tyr-Met-Val-[D-Nle] (SEQ ID NO: 7), c. Trp-Lys-Tyr-Met-Val-[D-Hse(Me)] (SEQ ID NO: 8), d. Trp-Lys-Tyr-Met-Val-[D-Ser(Me)] (SEQ ID NO: 9), e. Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 10), f. [1-Nal]-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 11), g. Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO: 37),67P7348PC00 h. Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 38), i. Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 39), j. Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 40), k. Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 41), l. Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 42), m. Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 43), n. Trp-Lys-Tyr-Nle-[Pro(4NH2)][D-Nle] (SEQ ID NO: 44), o. Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 45), p. Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 46), q. Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 47), r. Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 48), or s. Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 49), and a conjugated moiety (M) comprising or consisting of an acyl group selected from COOH(CH2)i4CO-, COOH(CH2)i6CO-, COOH(CH2)I8CO- and COOH(CH2)20CO, preferably COOH(CH2)I6CO- or COOH(CH2)I8CO-, more preferred COOH(CH2)i6CO-.

68. The compound according to any one of the preceding claims, wherein the compound comprises a peptide (P) consisting of any one of SEQ ID NO: 6-11 and 37-49, or a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of the peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX3 to XX5 of said peptide, such as a functional variant of any one of SEQ ID NO: 6-11 and 37-49 having 1 amino acid substitution in any one of positions XX1 or XX5 of said peptide; and a conjugated moiety (M) comprising or consisting of an acyl group selected from COOH(CH2)I4CO-, COOH(CH2)I6CO-, COOH(CH2)I8CO- and68P7348PC00COOH(CH2)2OCO, preferably COOH(CH2)I6CO- or COOH(CH2)I8CO-, more preferred COOH(CH2)ieCO.

69. The compound according to any one of claims 1 to 10, wherein said compound further comprises a linking group (L).

70. The compound according to any one of the preceding claims, wherein the conjugated moiety (M) is attached to the N-terminus of said peptide (P) via the linking group (L).

71. The compound according to any one of the preceding claims, wherein the conjugated moiety is attached to XX1 of said peptide via the linking group.

72. The compound according to any one of the preceding claims, wherein the conjugated moiety and / or the linking group is attached via an amide bond.

73. The compound according to any one of the preceding claims, wherein the linking group comprises or consists of at least one, such as one, linker compound selected from yGlu, PEG8, Gly or OEG.

74. The compound according to any one of the preceding claims, wherein the linking group comprises or consists of more than one linker compounds individually selected from yGlu, PEG8, Gly or OEG.

75. The compound according to any one of the preceding claims, wherein the linking group comprises or consists of one or more yGlu, such as 1 , 2, 3, 4 or 5 yGlu.

76. The compound according to any one of the preceding claims, wherein the linking group comprises or consists of one or more PEG8, such as 1 , 2, 3, 4 or 5 PEG8.

77. The compound according to any one of the preceding claims, wherein the linking group comprises or consists of one or more Gly, such as 1 , 2, 3, 4 or 5 Gly.69P7348PC0078. The compound according to any one of the preceding claims, wherein the linking group comprises or consists of one or more OEG, such as 1 , 2, 3, 4 or 5 OEG.

79. The compound according to any one of the preceding claims, wherein the linking group comprises or consists of: a. yGlu-Gly-Gly, b. [PEG8]-Gly-Gly, c. yGlu-[PEG8]-Gly-Gly, d. yGlu-[OEG]-[OEG], e. yGlu-[OEG]-[OEG]-Gly-Gly, or f. yGlu-[OEG]-[OEG]-[OEG]-[OEG]-Gly-Gly.

80. The compound according to any one of the preceding claims, wherein the compound comprises or consists of: a. [C18DA]-yGlu-[PEG8]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 19), b. [C18DA]-yGlu-[OEG][OEG][OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D- Nle] (SEQ ID NO: 20), c. [C18DA]-yGlu-[OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 21), d. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 22), e. [C18DA]-yGlu-[OEG][OEG]-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO:23), f. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO:24), g. [C18DA]-yGlu-Gly-Gly-Trp-Arg-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 25), h. [C18DA]-yGlu-Gly-Gly-Trp-[Lys(Ac)]-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 26), i. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-Val-[D-Nle] (SEQ ID NO: 27), j. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-Val-[D-Nle] (SEQ ID NO: 28), k. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Ser-[D-Nle] (SEQ ID NO: 29), l. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 30),70P7348PC00 m. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-[Pro(4NH2)][D-Nle] (SEQ ID NO: 31), n. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Tyr-[D-Nle] (SEQ ID NO: 32), o. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 33), p. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-[Hyp]-[D-Nle] (SEQ ID NO: 34), q. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Trp-Nle-Tyr-[D-Nle] (SEQ ID NO: 35), or r. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Arg-Nle-Tyr-[D-Nle] (SEQ ID NO: 36).

81. The compound according to any one of the preceding claims, wherein the compound comprises or consists of a compound selected from any one of SEQ ID NO: 19-36, or a functional variant of any one of SEQ ID NO: 19-36 having 1 amino acid substitution in any one of positions XX1 to XX6 of said peptide (P), such as a functional variant of any one of SEQ ID NO: 19-36 having 1 amino acid substitution in any one of positions XX1 to XX5 of said peptide (P), such as a functional variant of any one of SEQ ID NO: 19-36 having 1 amino acid substitution in any one of positions XX1 , XX2, XX3 or XX5 of said peptide (P), such as a functional variant of any one of SEQ ID NO: 19-36 having 1 amino acid substitution in any one of positions XX3 to XX5 of said peptide (P), such as a functional variant of any one of SEQ ID NO: 19-36 having 1 amino acid substitution in any one of positions XX1 orXX5 of said peptide (P).

82. The compound according to any one of the preceding claims, wherein the compound comprises or consists of: a. [C18DA]-yGlu-[PEG8]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 19), b. [C18DA]-yGlu-[OEG][OEG][OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D- Nle] (SEQ ID NO: 20), c. [C18DA]-yGlu-[OEG][OEG]-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 21), d. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 22), e. [C18DA]-yGlu-[OEG][OEG]-Trp-Lys-Tyr-Nle-Val-[D-Nle] (SEQ ID NO: 23), or71P7348PC00 f. [C18DA]-yGlu-Gly-Gly-Trp-Lys-Tyr-Nle-Val-[D-Hse(Me)] (SEQ ID NO: 24).

83. The compound according to any one of the preceding claims, wherein said compound binds and / or activates one or more of Formyl Peptide Receptor 1 (FPR1) and Formyl Peptide Receptor 2 (FPR2).

84. The compound according to any one of the preceding claims, wherein said compound binds and / or activates FPR2.

85. The compound according to any one of the preceding claims, wherein said compound is capable of binding to and / or activating FPR2.

86. The compound according to any one of the preceding claims, wherein said compound has binding affinity, efficacy and / or potency for FPR2, such as wherein said efficacy or potency for FPR2 is measured as FPR2 (Ca2+) ECso and / or FPR2 (cAMP) EC50.

87. The compound according to any one of the preceding claims, wherein said compound has a FPR2 (Ca2+) ECso of 0.001 to 3000 nM, such as 0.01 to 2000 nM, such as 0.1 to 1000 nM, such as 0.1 to 100 nM, such as 0.1 to 50 nM.

88. The compound according to any one of the preceding claims, wherein said compound has a FPR2 (Ca2+) ECso of 0.1 to 20 nM, such as 0.1 to 15 nM, such as 0.1 to 14 nM, such as 0.1 to 13 nM, such as 0.1 to 12 nM, such as 0.1 to 11 nM, such as 0.1 to 10 nM, such as 0.1 to 9 nM, such as 0.1 to 8 nM, such as 0.1 to 7 nM, such as 0.1 to 6 nM, such as 0.1 to 5 nM, such as 0.1 to 4 nM, such as 0.1 to 3 nM, such as 0.1 to 2 nM, such as 0.1 to 1 nM, such as 0.1 to 0.5 nM.

89. The compound according to any one of the preceding claims, wherein said compound has a FPR2 (Ca2+) ECso of 0.2 to 15 nM, such as 0.5 to 15 nM, such as 1 to 15 nM, such as 2 to 15 nM, such as 3 to 15 nM, such as 4 to 15 nM, such as 5 to 15 nM, such as 6 to 15 nM, such as 7 to 15 nM, such as 8 to 1572P7348PC00 nM, such as 9 to 15 nM, such as 10 to 15 nM, such as 11 to 15 nM, such as 12 to 15 nM, such as 13 to 15 nM, such as 14 to 15 nM.

90. The compound according to any one of the preceding claims, wherein said compound has a FPR2 (Ca2+) ECso of 1 to 10 nM, such as 2 to 9 nM, such as 3 to 8 nM, such as 4 to 7 nM, such as 4 to 6 nM, such as 5 to 6 nM.

91. The compound according to any one of the preceding claims, wherein said compound has a FPR2 (Ca2+) ECso of 1 to 5 nM, such as 1 to 4 nM, such as 1 to 3 nM, such as 2 to 3 nM.

92. The compound according to any one of the preceding claims, wherein said compound has a FPR2 (Ca2+) ECso of 0.005 to 1 nM, such as 0.01 to 1 nM, such as 0.015 to 1 nM, such as 0.02 to 1 nM, such as 0.025 to 1 nM, such as 0.03 to 1 nM, such as 0.035 to 1 nM, such as 0.04 to 1 nM, such as 0.045 to 1 nM, such as 0.05 to 1 nM, such as 0.055 to 1 nM, such as 0.06 to 1 nM, such as 0.065 to 1 nM, such as 0.07 to 1 nM, such as 0.075 to 1 nM, such as 0.08 to 1 nM, such as 0.085 to 1 nM, such as 0.09 to 1 nM, such as 0.095 to 1 nM.

93. The compound according to any one of the preceding claims, wherein said compound has a FPR2 (cAMP) ECso of 0.005 to 1 nM, such as 0.01 to 1 nM, such as 0.015 to 1 nM, such as 0.02 to 1 nM, such as 0.025 to 1 nM, such as 0.03 to 1 nM, such as 0.035 to 1 nM, such as 0.04 to 1 nM, such as 0.045 to 1 nM, such as 0.05 to 1 nM, such as 0.055 to 1 nM, such as 0.06 to 1 nM, such as 0.065 to 1 nM, such as 0.07 to 1 nM, such as 0.075 to 1 nM, such as 0.08 to 1 nM, such as 0.085 to 1 nM, such as 0.09 to 1 nM, such as 0.095 to 1 nM.

94. The compound according to any one of the preceding claims, wherein said compound has a FPR2 (cAMP) ECso of 1 to 20 nM, such as 1 to 15 nM, such as 1 to 14 nM, such as 1 to 13 nM, such as 1 to 12 nM, such as 1 to 10 nM, such as 1 to 9 nM, such as 1 to 8 nM, such as 1 to 7 nM. such as 1 to 6 nM, such as1 to 5 nM, such as 1 to 4 nM, such as 1 to 3 nM, such as 1 to 2 nM.73P7348PC0095. The compound according to any one of the preceding claims, wherein said compound has different affinities and / or receptor activation efficacies for FPR1 and FPR2.

96. The compound according to any one of the preceding claims, wherein said compound is FPR2 selective.

97. The compound according to any one of the preceding claims, wherein said compound has higher selectivity for FPR2 than FPR1.

98. The compound according to any one of the preceding claims, wherein said compound has at least 2 fold higher selectivity for FPR2 than for FPR1 , such as at least 3 fold, such as at least 4 fold, such as at least 5 fold, such as at least 6 fold, such as at least 7 fold, such as at least 8 fold, such as at least 9 fold, such as at least 10 fold, such as at least 15 fold, such as at least 20 fold, such as at least 25 fold, such as at least 30 fold, such as at least 40 fold, such as at least 50 fold, such as at least 60 fold, such as at least 70 fold, such as at least 80 fold, such as at least 90 fold, such as at least 100 fold higher selectivity for FPR2 than for FPR1.

99. The compound according to any one of the preceding claims, wherein said compound more than 100 fold higher selectivity for FPR2 than for FPR1 , such as more than 200 fold, such as more than 300 fold, such as more than 400 fold, such as more than 500 fold, such as more than 600 fold, such as more than 700 fold, such as more than 800 fold, such as more than 900 fold, such as more than 1000 fold, such as more than 1100 fold, such as more than 1200 fold, such as more than 1300 fold, such as more than 1400 fold, such as more than 1500 fold, such as more than 1600 fold, such as more than 1700 fold, such as more than 1800 fold, such as more than 1900 fold, such as more than 2000 fold higher selectivity for FPR2 than for FPR1.

100. The compound according to any one of the preceding claims, wherein said compound has a 400 to 500 fold higher selectivity for FPR2 than for FPR1 , such as 410 to 490, such as 420 to 480, such as 430 to 480, such as 430 to74P7348PC00470, such as 430 to 460, such as 430 to 450, such as 435 to 450, such as 435 to 445 fold higher selectivity for FPR2 than for FPR1.

101. The compound according to any one of the preceding claims, wherein said compound has 10 to 500 fold higher selectivity for FPR2 than for FPR1, such as 10 to 400 fold, such as 10 to 300 fold, such as 10 to 250 fold, such as 10 to 200 fold, such as 10 to 150 fold, such as 10 to 100 fold, such as 10 to 90 fold, such as 10 to 80 fold, such as 10 to 70 fold, such as 10 to 60 fold, such as 10 to 50 fold, such as 10 to 40 fold, such as 10 to 30 fold, such as 10 to 20 fold higher selectivity for FPR2 than for FPR1102. The compound according to any one of the preceding claims, wherein said compound has 10 to 250 fold higher selectivity for FPR2 than for FPR1, such as 10 to 230 fold, such as 10 to 200 fold, such as 10 to 150 fold, such as 10 to 100 fold, such as 10 to 90 fold, such as 10 to 80 fold, such as 10 to 70 fold, such as 10 to 60 fold, such as 10 to 50 fold, such as 10 to 40 fold, such as 10 to 30 fold, such as 10 to 20 fold higher selectivity for FPR2 than for FPR1.

103. The compound according to any one of the preceding claims, wherein said compound has 50 to 150 fold higher selectivity for FPR2 than for FPR1, such as 60 to 140 fold, such as 70 to 130 fold, such as 80 to 120 fold, such as 90 to 120 fold, such as 100 to 120 fold, such as 110 to 120 fold, such as 110 to 115 fold higher selectivity for FPR2 than for FPR1.

104. The compound according to any one of the preceding claims, wherein said compound has 10 to 50 fold higher selectivity for FPR2 than for FPR1, such as 11 to 45 fold, such as 12 to 40 fold, such as 13 to 35 fold, such as 14 to 30 fold, such as 15 to 35 fold, such as 16 to 20 fold higher selectivity for FPR2 than for FPR1.

105. The compound according to any one of the preceding claims, wherein said compound has 1 to 40 fold higher selectivity for FPR2 than for FPR1 , such as 1 to 39 fold, such as 2 to 40 fold, such as 3 to 40 fold, such as 4 to 40 fold, such as 4 to 35 fold, such as 4 to 30 fold, such as 4 to 40 fold, such as 5 to 40 fold, such as 5 to 35 fold, such as 5 to 30 fold, such as 5 to 25 fold, such as 1075P7348PC00 to 20 fold, such as 11 to 21 fold, such as 11 to 19 fold higher selectivity for FPR2 than for FPR1.

106. The compound according to any one of the preceding claims, wherein said compound has 1 to 20 fold higher selectivity for FPR2 than for FPR1 , such as 1 to 19 fold, such as 1 to 18 fold, such as 1 to 17 fold, such as 1 to 16 fold, such as 1 to 15 fold, such as 1 to 14 fold, such as 1 to 13 fold, such as 1 to 12 fold, such as 1 to 11 fold, such as 1 to 10 fold, such as 1 to 9 fold, such as 1 to 8 fold, such as 1 to 7 fold, such as 1 to 6 fold, such as 1 to 5 fold, such as 1 to 4 fold, such as 1 to 3 fold, such as 1 to 2 fold higher selectivity for FPR2 than for FPR1.

107. The compound according to any one of the preceding claims, wherein said higher selectivity for FPR2 than for FPR1 is measured as binding affinity, efficacy and / or potency for FPR2 compared to binding affinity, efficacy and / or potency for FPR1.

108. The compound according to any one of the preceding claims, wherein said higher selectivity for FPR2 than for FPR1 is measured as potency for FPR2 compared to potency for FPR1 .

109. The compound according to any one of the preceding claims, wherein said higher selectivity for FPR2 than for FPR1 is measured as FPR2 (Ca2+) ECso and / or FPR2 (cAMP) EC50 compared to FPR1 (Ca2+) EC50 and / or FPR1 (cAMP) EC50.

110. The compound according to any one of the preceding claims, wherein said higher selectivity for FPR2 than for FPR1 is measured as FPR2 (Ca2+) EC50 compared to FPR1 (Ca2+) EC50.

111. The compound according to any one of the preceding claims, wherein said compound preferentially activates the Ca2+ pathway.

112. The compound according to any one of the preceding claims, wherein said compound preferentially activates the cAMP pathway.76P7348PC00113. The compound according to any one of the preceding claims, wherein said compound has a Ca2+ / cAMP bias factor of -3 to +1 , such as -2.5 to +0.5, such as -2.5 to 0, such as -2. to 0, such as -1.5 to -0.5.

114. The compound according to any one of the preceding claims, wherein said compound has a Ca2+ / cAMP bias factor of -3 to 0, such as -2.5 to 0, such as -2.5 to -0.5, such as -2.5 to -1.

115. The compound according to any one of the preceding claims, wherein said compound has a Ca2+ / cAMP bias factor of 0 to 1 , such as 0 to 0.8, such as 0 to 0.5, such as 0 to 0.3.

116. The compound according to any one of the preceding claims, wherein the Ca2+ / cAMP bias factor is calculated as Alog(Emax / EC50) Ca2+ pathway - Alog(Emax / EC50) cAMP pathway.

117. A pharmaceutical composition comprising a compound according to any one of the preceding claims.

118. A pharmaceutical composition comprising a compound according to any one of the preceding claims comprising a pharmaceutically acceptable excipient, such as a carrier, an adjuvant and / or a diluent.

119. A compound or a pharmaceutical composition according to any one of the preceding claims for use as a medicament.

120. A compound or a pharmaceutical composition according to any one of the preceding claims for use in the treatment of chronic inflammation.

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