550results about "Peptides with abnormal peptide link" patented technology

A hydrophilic linker, an intermediate of the hydrophilic linker, a linker-drug conjugate prepared from the linker and a preparation method therefor, and an antibody-drug conjugate and use thereof.

The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of membrane type 1 metalloprotease (MT1-MMP). The invention also describes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups which have utility in imaging and targeted cancer therapy.

An antibody-drug conjugate as shown in formula I, a preparation method therefor, and a use thereof in prevention and / or treatment of diseases related to abnormal cell activity, including but not limited to a use in prevention and / or treatment of tumor diseases.

To provide camptothecin compounds and their conjugates with novel structures, improved efficacy and improved safety.SOLUTION: The present invention provides a compound having the structure of the upper formula in the figure, or a pharmaceutically acceptable salt, ester, stereoisomer, polymorph, solvate, nitrogen oxide, isotope-labeled product, metabolite or prodrug thereof. In the formula, R1 and R2 are each hydrogen, halogen, C1-6 alkyl, C1-6 alkoxyl, or the like, or are connected with adjacent carbon atoms to form a 5- to 6-membered oxygen-containing heterocyclic ring; R3 is hydrogen or is connected with an ortho-carbon atom of R1 to form a 6-membered carbocyclic ring; and A is selected from one of the lower two formulas in the figure.SELECTED DRAWING: None

The present disclosure provides a compound comprising a radiolabeling moiety, a targeting moiety, and a DNA intercalating agent and complexes thereof For example, the present disclosure provides a compound of Formula I or a pharmaceutically acceptable salt and / or solvate thereof. Methods of making and uses thereof, such as cancer theranostic applications, are also included. (I)

Provided herein are compounds, compositions, and methods for the treatment of diseases and disorders associated with liver X receptors, comprising bis-octahydrophenanthrenecarboxamides and protein (e.g., antibody) drug conjugates thereof. [Selected figure] Figure 11

The present invention relates to a compound binding to an endogenous receptor, said compound comprising (i) an oligopeptide comprising a dipeptide with Trp being the C-terminal amino acid of said dipeptide, wherein said Trp is replaced with an α-amino acid Xaa2, whereby the stability in serum or plasma of the peptide bond connecting Xaa2 to the N-terminally adjacent amino acid is increased as compared to the peptide bond connecting Trp to the N-terminally adjacent amino acid in an otherwise identical compound; and (ii) a moiety capable of generating therapeutically effective radiation, said moiety being covalently bound to said oligopeptide.

Methods and devices for the administration of compositions comprising glutathione trisulfide (GSSSG), pantethine trisulfide (PTN-SSS), or lipoic acid trisulfide (LA-SSS) to treat peripheral neuropathy, e.g., chemotherapy-induced peripheral neuropathy (CIPN), e.g., by oral or nasal administration. The methods can be used, e.g., to reduce pain associated with CIPN, or reduce the risk of development of CIPN.

The present application provides stable peptide-based Akt capture agents and the use thereof as detection, diagnosis, and treatment agents. The application further provides novel methods of developing stable peptide-based capture agents, including Akt capture agents, using iterative on-bead in situ click chemistry.

The invention relates to a method for semi-solid-phase synthesis of a polycyclic compound and an intermediate, a long chain is synthesized through solid phase, then two-step ring closing is performed to form a key intermediate, and simple derivation is performed on the basis of the key intermediate to obtain a PCSK9 antagonist compound. According to the invention, starting materials for solid-phase synthesis are selected, steric hindrance is effectively avoided, and solid-phase reaction and subsequent liquid-phase correlation cyclization can be smoothly carried out, so that the yield is improved, and the cost is reduced.

To provide camptothecin compounds and their conjugates with novel structures, improved efficacy and improved safety.SOLUTION: The present invention provides a compound having the structure of the upper formula in the figure, or a pharmaceutically acceptable salt, ester, stereoisomer, polymorph, solvate, nitrogen oxide, isotope-labeled product, metabolite or prodrug thereof. In the formula, R1 and R2 are each hydrogen, halogen, C1-6 alkyl, C1-6 alkoxyl, or the like, or are connected with adjacent carbon atoms to form a 5- to 6-membered oxygen-containing heterocyclic ring; R3 is hydrogen or is connected with an ortho-carbon atom of R1 to form a 6-membered carbocyclic ring; and A is selected from one of the lower two formulas in the figure.SELECTED DRAWING: None

To provide STAT degraders and uses thereof.SOLUTION: The present invention provides compounds, compositions thereof, and methods of using the compositions. In some embodiments, the present invention provides a method of treating a hematologic malignancy selected from LGL leukemia (T cell and NK cell), cutaneous T cell lymphoma (CTCL), peripheral T cell lymphomas (PTCL, all subtypes including ALCL), diffuse large B cell lymphoma (DLBCL), acute myelogenous leukemia, multiple myeloma, and myelofibrosis.SELECTED DRAWING: None

The invention discloses a cell adhesion protein Nectin-4 targeted bicyclic peptide fluorescent probe and a preparation method thereof, the probe provided by the invention can be used for accurate detection of recurrent tumors and metastatic lymph nodes, and the probe is applied to rapid pathology and fluorescent surgical navigation in an operation. The method has the advantages of high signal-to-background ratio, high specificity and long imaging time window.

According to an embodiment of the present invention, there is provided a magnetic resonance image processing method, the magnetic resonance image processing method being performed by a magnetic resonance image processing apparatus, the magnetic resonance image processing method including: inputting an input image having a slice resolution higher than 0 and lower than 1 to an artificial neural network model; and outputting an output image having a slice resolution of 1 from the artificial neural network model.

The invention belongs to the field of medicines, and discloses an SERPINE1 protein degradation agent and application thereof. The general formula of the SERPINE1 protein degradation agent is # imgabs0 # or # imgabs1 #. The research finds that a structural fragment for inhibiting SERPINE1 protein and a structural sheet or a hydrophobic label of an E3 protein ligand are coupled together through a linker, the length of the linker is adjusted, the obtained SERPINE1 protein degradation agent has an unexpected anti-tumor effect, the anti-tumor effect of the SERPINE1 protein degradation agent is superior to that of a single SERPINE1 inhibitor, and the SERPINE1 protein degradation agent has a good application prospect. The drug resistance of tumor cells can be overcome, and the drug-forming target property is good.

The invention relates to application of a topoisomerase inhibitor and a conjugate thereof. Specifically, the inventor provides a class of camptothecin derivatives, linker conjugates and antibody-drug conjugates with novel structures, and the camptothecin derivatives, linker conjugates and antibody-drug conjugates have excellent anti-tumor activity and good lipophilicity. In-vitro and in-vivo experiments show that the drug conjugate containing the camptothecin derivative disclosed by the invention has an improved anti-tumor curative effect and high safety, and has an application prospect in the field of cancer treatment.

A compound comprising a prostate specific membrane antigen (PSMA)-targeting moiety of the following formula (I) or of a salt or a solvate thereof. R1 is —R1aR1b— wherein R1a is absent, —CH2—, —O—, or —S—, and R1b is —CH2— or —CHF—. R2 is —(CH2)3—O—, —(CH2)3—, —(CH2)4—, —CH2—O—(CH2)2—, or —CH2—S—(CH2)2. R3 is ethylene fused to a tricyclic fused ring. L1, L2, L3, L4, L5b L5c, L6 and L7 are linkages (e.g. peptide bonds). Xbr is a branching atom. Rrad is a radiometal chelator. Ralb is an albumin binder. n1, n2, n3, n4, and n5 are integers. When the PSMA-targeting moiety is linked to a radiolabeling group, the compound may be used as an imaging agent or therapeutic agent for PSMA-expressing diseases / conditions.

The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of membrane type 1 metalloprotease (MT1-MMP). The invention also describes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups which have utility in imaging and targeted cancer therapy.

The invention relates to an azobenzene-containing connexon as shown in a formula I, a protein coupling medicine containing the connexon and application of the connexon, further relates to a pharmaceutical composition containing the protein coupling medicine, and further relates to application of the protein coupling medicine for treating and / or preventing diseases. # imgabs0 #

To provide non-natural amino acids and dolastatin analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides.SOLUTION: The dolastatin analogs may have a wide range of possible functional groups, but typically have at least one oxime, carbonyl, dicarbonyl, and / or hydroxylamine group. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and / or hydroxylamine group.SELECTED DRAWING: Figure 4

The present application relates to polypeptides having carnosine synthase activity; a polynucleotide encoding the polypeptide; a microorganism comprising any one or more of the polypeptide, the polynucleotide, and a vector comprising the polynucleotide; variant polypeptides having carnosine synthase activity; a polynucleotide encoding the variant polypeptide; a microorganism comprising any one or more of the variant polypeptide, the polynucleotide, and a vector comprising the polynucleotide; a composition for producing carnosine, the composition comprising any one or more of a polypeptide having carnosine synthase activity, the variant polypeptide, the microorganism, and a culture product of the microorganism; a method for producing carnosine using any one or more of a polypeptide having carnosine synthase activity, the variant polypeptide, and the microorganism; and polypeptides having carnosine synthase activity, the use of the variant polypeptides and the microorganisms for the production of carnosine.

The invention discloses a peptidomimetic compound as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. The peptidomimetic compound is shown as a formula I in the specification. The compound can act on the nerve center, has anti-epilepsy and anti-depression effects, can also act on the gastrointestinal tract, inhibits gastric acid secretion or tumor cell growth, is a novel cholecystokinin type 2 receptor antagonist, and has a great application prospect.

The present invention relates to the technical field of medicines and disclosed are a neuroprotective polypeptide compound and an application thereof. The neuroprotective polypeptide compound comprises a polypeptide having the following chemical formula and a salt thereof: (M)m-(Lys-Leu-Ser-Ser-Ile-Glu / Asp-Ser / Thr-Asp / Glu-Val / Leu)-(N)n; m and n are integers from 0 to 3, but m and n are not zero at the same time; M is beta-Ala-His, beta-Ala-1-Methyl-His or beta-Ala-3-Methyl-His, and N is beta-Ala-His, beta-Ala-1-Methyl-His or beta-Ala-3-Methyl-His. An intravenous dosage of only 3 mg / kg can unexpectedly achieve a significant therapeutic effect and achieve the same effect as NA1. The polypeptide compound can be used in combination with a hemolytic drug to provide a new possibility for the treatment of stroke.

The application discloses a pyrrolobenzodiazepine-anthracene imide hybrid molecule and a preparation method and application thereof, and belongs to the technical field of chemical medicines. In order to solve the problems of few kinds of warheads of an existing antibody drug conjugate, single action mechanism and drug resistance easily generated in long-term use, a pyrrolobenzodiazepine-anthracene imide hybrid molecule shown in formula I and a preparation method and application thereof are provided. Experimental results show that the compound has strong anti-proliferation activity in various tumor cells such as ovarian cancer cells, gastric cancer cells and breast cancer cells, and an antibody drug conjugate thereof has good in-vivo and in-vitro anti-tumor activity and good safety.

Provided herein are compositions, such as suitable for subcutaneous administration, and methods for treating ascites in a subject using a hybrid V1A receptor agonist-antagonist.

The present disclosure provides for polypeptide conjugates. The polypeptide conjugates disclosed herein comprise a polyarginine peptide and a cyclic cell-penetrating peptide (cCPP) conjugated, directly or indirectly, to the polyarginine peptide. The present disclosure demonstrates that cCPPs conjugated to polyarginine peptides can be used to deliver nucleic acids to the cytosol of cells.

Described herein are anti-NaPi2b antibody-drug conjugates (ADCs) comprising an antibody construct that binds to human sodium-dependent phosphate transporter 2B (NaPi2b) conjugated to a camptothecin analog of Formula (I). The antibody construct of the ADC comprises an amino acid modification in the Fc that knocks out binding to Fc gamma receptors. The ADCs are useful as therapeutic agents, among others, in the treatment of cancer.

The present disclosure provides calcium-sensing receptor agonist compounds and uses thereof. Specifically, the present disclosure provides a series of polypeptide calcium-sensing receptor agonist compounds and pharmaceutical compositions of pharmaceutically acceptable salts thereof that have agonistic activity against the human calcium-sensing receptor (CaSR), thereby lowering plasma parathyroid hormone and serum calcium ion levels, and can be used to treat metabolic diseases such as primary hyperparathyroidism, secondary hyperparathyroidism, and tumor-induced hypercalcemia.

Compounds for targeting and agents for imaging, prostate-specific membrane antigen (PSMA) are disclosed. Methods of synthesizing compounds and imaging agents, as well as methods for imaging PSMA are also disclosed. The imaging agents disclosed are suitable for PET and SPECT imaging.