933results about "Peptides with abnormal peptide link" patented technology

The present invention relates to four specific macrocyclic compounds for use as inhibitors of KRAS mutant for the treatment of cancer. Example (1): 1-[4-(dimethylamino)-4-methyl-pent-2-ynoyl]-N-[(1S)-1-[[(6S,8S,14S)-22-ethyl-25-fluoro-(21M)-21-[2-[(1S)-1-methoxyethyl]-3-pyridyl]-18,18-dimethyl-9,15-dioxo-5,16-dioxa-2,10,22,28-tetrazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),20,23(27),24-tetraen-8-yl]carbamoyl]-2-methyl-propyl]-4-fluoro-N-methyl-piperidine-4-carboxamide.

The invention discloses a compound represented by a formula (1), or a tautomer, a mesomer, a raceme, an enantiomer, a diastereoisomer, or a mixture form thereof, or a pharmaceutically acceptable salt, a prodrug or a solvate thereof, the structure of the formula (1) is represented as follows: # imgabs0. Strong hydrophilic sulfonic acid inner salt and / or phosphoric acid inner salt side chains are introduced at the position of (AAA and the like)-PAB (self-destruction group), so that the druggability (including hydrophilicity and stability) of the antibody drug conjugate corresponding to the compound is greatly enhanced, the in-vivo drug removal effect is reduced, and the tumor treatment effect is improved.

A compound represented by formula (1), or a tautomer, mesomer, racemate, enantiomer, and diastereomer thereof, or mixture form thereof, or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein the structure of formula (1) is as shown below: formula (1). According to the compound, a strong hydrophilic sulfonate inner salt and / or phosphate inner salt side chain are introduced at the position of polypeptide (VC, VA, AAA, etc.)-PAB (self-immolative group) of a linker, greatly enhancing the druggability (comprising hydrophilicity and stability) of an antibody drug conjugate corresponding to the compound, reducing the in-vivo drug clearance effect, and improving the tumor treatment effect.

The invention relates to an arteannuic acid derivative as well as a preparation method and application thereof, the arteannuic acid derivative comprises water-soluble organic salt formed by reaction of arteannuic acid or dihydroarteannuic acid and small molecular alkaline organic matter, or water-soluble complex formed by reaction of arteannuic acid or dihydroarteannuic acid and small molecular peptide, or water-soluble complex formed by reaction of arteannuic acid or dihydroarteannuic acid and small molecular peptide. The arteannuic acid or the dihydroarteannuic acid reacts with an alkaline metal compound to form a water-soluble salt. The arteannuic acid derivative provided by the invention solves the problem that arteannuic acid and dihydroarteannuic acid are insoluble in water, has the biological activity of whitening, anti-inflammatory and anti-tumor, and has good research and development prospects.

The present disclosure relates to peptide compounds of Formula A, A-II, A-III, A-III, A-IV, B, or C, or a salt or solvate thereof, compositions thereof, and methods of use thereof. The compounds of the present disclosure are useful for targeting CXCR4 for purposes such as imaging and / or therapy.

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and / or presenter proteins are intracellular proteins. In some embodiments, the target and / or presenter proteins are mammalian proteins.

It is an object of the present invention to provide drugs that bind specifically to FAPα, are effective in the treatment and diagnosis of tumors or cancers expressing FAPα, for example, in the treatment and diagnosis of solid cancers such as pancreatic cancer, sarcoma, esophageal cancer, lung cancer, breast cancer, prostate cancer, head and neck cancer, ovarian cancer, colon cancer, neuroendocrine tumor, thyroid cancer, uterine cancer, liver cancer and the like (particularly, pancreatic cancer), and have a lower risk of prolonged side effects. The present invention provides a conjugate comprising a radioactive moiety comprising an aryl group substituted with a radionuclide selected from 211At, 210At, 131I, 125I, 124I, 123I, 77Br and 76Br, and a bioactive moiety having an affinity for fibroblast activation protein α (FAPα).

Compounds are provided include a. cyclic cell penetrating peptide (cCPP) and one or more linkers comprising, an amino acid component, a. polyethylene glycol component, a hydrophobic component, or a combination thereof. In embodiments, the compound includes an exocyclic peptide (EP). In embodiments, the compound does not include an exocyclic peptide.

The present application relates to a compound or a pharmaceutically acceptable salt and / or solvate thereof comprising one or more circulation enhancing groups, one or more target binding groups, one or more chelating groups, at one least cleavable linker and at least one branching group that is at least trivalent. The application further includes a radionuclide complex or a pharmaceutically acceptable salt and / or solvate thereof, comprising a compound of the application or a pharmaceutically acceptable salt and / or solvate thereof, and one or more radionuclides, and to compositions comprising the compound or the complexes. The present application also includes methods of using the compounds, complexes and compositions for targeting and / or killing target cells. For example, the compound includes a compound of Formula I

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.

The invention relates to the field of bioconjugation of functional entities, such as payloads and targeting agents, mediated by novel trans-cyclooctene (TCO) compounds. More particularly the present invention relates to novel trans-cyclooctene compounds, unnatural amino acids comprising such trans-cyclooctene compounds and preparation thereof. Said novel trans-cyclooctene compounds and unnatural amino acids comprising such trans-cyclooctene compounds are characterized by high structural stability and hydrophilicity and thus instrumental to ease the conjugation of said functional entities. The invention further relates to respective trans-cyclooctene-functionalized construct obtainable by, in particular covalently, binding said novel trans-cyclooctene compounds to a targeting agent or payload molecule, said functionalized construct containing at least one functionalizing residue comprising a mono-unsaturated trans-cyclooctene entity. The invention further relates to conjugates obtainable by covalently linking, in particular, via biorthogonal bioconjugation via a Diels-Alder-type cycloaddition, a first functionalized molecule, particularly selected from said trans-cyclooctene-functionalized constructs with a second functionalized molecule comprising a docking group (DG) capable of reacting with the trans-cyclooctene-type functional group of the first functionalized molecule. The present invention further relates to preparation methods of said constructs and conjugates. The invention also relates to the use of such conjugates of the present invention for use in medicine, to corresponding pharmaceutical compositions as well as to corresponding diagnostic and analytical kits.

The invention provides polar units, linker intermediates, linkers, drug linkers and conjugates thereof.

The invention relates to an acinetobacter baumannii resistant cyclic peptide and application thereof, in particular to a compound shown in a formula (I), a tautomer, a stereoisomer, a hydrate, a solvate, pharmaceutically acceptable salt or prodrug of the compound and a preparation method of the tautomer, the stereoisomer, the hydrate, the solvate and the pharmaceutically acceptable salt or prodrug of the compound. The invention further discloses application of the acinetobacter baumannii in preparation of drugs for treating or preventing infection and diseases caused by the acinetobacter baumannii. # imgabs0 #

The invention discloses a VEGF / TIE-2 dual-targeting polypeptide and application thereof in preparation of antitumor drugs, and relates to the technical field of biological medicines. The VEGF / TIE-2 dual-targeting polypeptide (named as RTP) provided by the invention is formed by combining an amino acid sequence capable of identifying VEGF and TIE-2 in a targeting manner, an amino acid sequence capable of forming beta-sheet nanofibers through self-assembly, an amino acid sequence capable of identifying carbonic anhydrase IX in a targeting manner and an enzyme reactive amino acid sequence capable of realizing MMP-2 specific shearing. The RTP can be subjected to allosteric and self-assembly in tumor cells to form stable water-insoluble nanofibers, the formation and metastasis of tumor neovascularization are strongly inhibited through VEGF and TIE-2 double signal channels, and the tumor progress is inhibited.

The present invention provides kappa opioid receptor peptide agonists, methods for preparing these compounds, compositions comprising these kappa opioid receptor peptide agonists, and methods of using the kappa opioid receptor peptide agonists to treat pain or other conditions.

The invention discloses a camptothecin micromolecule, an antibody drug conjugate thereof, a preparation method and an application. The invention provides a camptothecin micromolecule as shown in a formula I or a pharmaceutically acceptable salt thereof. The camptothecin micromolecule provided by the invention and the antibody drug conjugate thereof have good cytotoxic activity and can inhibit proliferation of tumor cells. # imgabs0 #

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.

The present invention relates to a WKYMVm peptide analog comprising an amino acid sequence of Trp (W)-Lys (K)-Tyr (Y)-Met (M)-Val (V)-D-Met (m), in which at least one amino acid residue selected from the group consisting of Lys (K), Tyr (Y), and Met (M) in the amino acid sequence is substituted with a β3-amino acid residue or a peptoid residue, and a use thereof. The WKYMVm peptide analogs of the present invention has effects of increasing stability by increasing in vivo degradation half-life and of promoting activation of innate immune responses by neutrophils through activation of formyl peptide receptors, and thus can be effectively used in preventing or treating a disease that is be prevented or treated by formyl peptide receptors, especially an infectious disease or inflammatory disease.

The invention provides a Nectin-4 targeting bicyclic peptide compound as shown in a formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof as a nuclide ligand, and belongs to the field of medicines. The invention also provides a complex containing the bicyclic peptide compound, the bicyclic peptide compound is further connected with radionuclide, a pharmaceutical composition containing the complex, and application of the complex and the pharmaceutical composition in preparation of drugs for preventing, treating, treating and / or alleviating cancers. # imgabs0 #

A compound comprising a prostate-specific membrane antigen (PSMA) targeting moiety of the following formula: R 0 is O or S. 1a , R 1b and R 1c Each of R may be, for example, —COH, —SOH, —SOH, —POH, or —POH. 2 R may be an optionally substituted methylene or a derivative thereof, propylene or a derivative thereof, or a derivative of ethylene. 3 is a linker. When the PSMA targeting moiety is attached to a radiolabeling group, the compound may be used as an imaging agent or a therapeutic agent for diseases / conditions that express PSMA. TIFF2022537773000240.tif2237

A camptothecin small molecule and an antibody drug conjugate thereof, a preparation method therefor and the use thereof. Provided is a camptothecin small molecule as shown in formula I or a pharmaceutically acceptable salt thereof. The provided camptothecin small molecule and the antibody drug conjugate thereof have a good cytotoxic activity, and can inhibit the proliferation of tumor cells.

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.

The present invention provides antibody drug conjugates, wherein an antibody or antibody fragment that specifically binds to human cKIT is linked to a drug moiety, optionally through a linker. The present invention further provides pharmaceutical compositions comprising the antibody drug conjugates; and methods of making and using such pharmaceutical compositions for ablating hematopoietic stem cells in a patient in need thereof.

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.

Among the various aspects of the present disclosure are compounds that are useful for inhibiting one or more proteases including various serine proteases such as Hepatocyte Growth Factor Activator (HGFA), and the type II transmembrane serine proteases (TTSPs) including matriptase, hepsin, and TMPRSS2. The present invention also relates to various methods of using the inhibitor compounds to treat and / or prevent infections and their symptoms / complications, including those caused by coronaviruses and influenza viruses, conditions associated with inflammation, various other malignancies, pre-malignant conditions, and / or cancer.

The invention belongs to the technical field of biological medicines, and discloses a small molecule ligand for targeted administration, a ligand medicine conjugate, a rheumatoid arthritis treatment medicine and application. The small molecule ligand for targeted administration provided by the invention takes a structure as shown in a formula (1) as a linker, and meanwhile, a group M1 derived from a fibroblast activating protein inhibitor is introduced, so that the small molecule ligand can be well applied as a drug delivery platform for RA treatment; the molecular biological activity of the anti-rheumatism medicine is kept, and meanwhile, the anti-rheumatism medicine is fully released in an inflammation joint area, so that a better rheumatoid arthritis treatment effect is achieved, and the anti-rheumatism medicine has a good application prospect. # imgabs0 #