203results 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 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.

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.

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.

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.

The application discloses a mutant of glutamate-cysteine synthetase and application of the mutant in synthesis of glutathione. Single-site mutation is carried out on amino acid residues at positions 150, 188, 235, 236, 241, 300, 301, 302 and 330 of wild-type glutamate-cysteine synthetase (Glutamate-cysteine ligase [EC:6.3.2.2]) from Citrobacter koseri (strain ATCC BAA-895), and mutant sites at positions 150, 236, 302 and 330 are screened. Mutants M1-M6 are obtained by combination mutation of the mutant sites screened above, and the enzyme activity of the mutant M4 with the highest activity is increased by 477% compared with that of the wild-type glutamate-cysteine synthetase. The mutant M4 is used to catalyze synthesis of glutathione, and the highest concentration reaches 23 g / L, which is increased by 4.2 times compared with the wild type, and the production cost is greatly reduced, so the mutant has important application value.

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 present application relates to the technical field of biomedicine, and in particular to a glutamate urea compound, a preparation method and a use thereof, a nuclide targeting probe, a preparation method and a use thereof, and a pharmaceutical composition. The glutamate urea compound and the nuclide targeting probe provided by the present application have excellent in vivo biological properties, high specific uptake in lesions having high PSMA protein expression, high target-to-non-target ratio, low non-specific background activity, and significantly enhanced tumor uptake and retention time, are suitable for use as nuclide treatment and imaging of tumors, can also reduce unnecessary radioactive damage to normal tissues and organs, can overcome the defects of relatively low target organ uptake and excessively short retention time of small molecules acting on PSMA, exhibit improved targeted PSMA nuclide treatment and imaging effects, and have the potential for clinical promotion and application.

The present invention relates to a peptide inhibitor of interleukin-23 receptor, and a use thereof. In particular, it relates to a peptide inhibitor of interleukin-23 receptor, a stereoisomer, pharmaceutically acceptable salt or solvate thereof, a pharmaceutical composition thereof, and a use of the peptide inhibitor in treating or preventing diseases or conditions comprising inflammatory bowel disease, Crohn's disease, and psoriasis.

The invention relates to the technical field of biological medicine, in particular to polypeptide for promoting release of growth hormone and application of the polypeptide, the polypeptide is shown as a formula (I), and in addition, the invention further provides application of the polypeptide shown as the formula (I) in preparation of medicine for diagnosing and / or treating diseases related to human growth hormone deficiency. Formula (I)

The present disclosure provides compounds and methods for preparing antibody conjugates with fluorophores, as well as methods of using these conjugates for cell imaging. In one embodiment, the conjugate can be bound to a quencher to absorb fluorescence from the fluorophore.

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

Provided are cyclic peptidomimetics that can, e.g., antagonize the extracellular domain of EGFR, and methods of use thereof.

Provided herein are compounds for delivery of one or more radiotherapeutic or radiodiagnostic agents. In some embodiments, the compounds have a radioactive agent binding moiety (RBM) connected to a GRPR binding moiety (GBM) through a linker (RBM-L-GBM), wherein the at least one of L and GBM is optionally substituted with an albumin binding moiety (ABM). In some embodiments, the one or more therapeutic or diagnostic agents are delivered to cancer cells.

The present invention provides a conjugate of an antibody and a functional substance, said conjugate having excellent desired properties, or a salt thereof. More particularly, the present invention provides a conjugate of an antibody and a functional substance, said conjugate containing a structural unit represented by formula (1) [wherein: Ig represents an immunoglobulin unit containing two heavy chains and two light chains and bonded to LA adjacent to Ig via thiol groups in the side chains of a plurality of cysteine residues in the two heavy chains and two light chains; HG represents a hydrophilic group or a monovalent group containing a hydrophilic group; CS represents a divalent group containing a cleavable moiety; ring A represents a divalent aromatic ring group which may have a substituent (wherein the divalent aromatic ring group constitutes a π-electron conjugated system together with the aforesaid cleavable moiety); V represents an oxygen atom, a sulfur atom or an amino(NH) group; LA and LB independently represent a divalent group; D represents a functional substance; and the average number n of the aforesaid bonds per immunoglobulin unit is 1.5 or more] or a salt thereof, and substances related thereto.

The present invention relates to a conjugate having the formula: CLA, or a pharmaceutically acceptable salt thereof, wherein C is a chelator, L is a linker covalently attached to the chelator, and A is a gastrin-releasing peptide receptor antagonist covalently attached to the linker, wherein the chelator has formula (I) where the dotted line represents the covalent bond to the linker; the linker has the formula: -β-Ala-β-Ala-; and the gastrin-releasing peptide receptor antagonist has the amino acid sequence: -DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2. The present invention also relates to uses of the conjugate or salt thereof. TIFF2023542218000025.tif72105

Provided herein are bispecific antigen-binding molecules that bind HER2 and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably nonoverlapping) epitopes of the extracellular domain of human HER2. The bispecific antigen-binding molecules cluster on the surface of HER2 IHC2+ and IHC3+ cells, and are internalized into the cellular lysosomes. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.

Disclosed are a new nanobody (Nb) targeting a tissue factor (TF) and a nanobody-drug conjugate (NDC), a preparation method therefor and the use thereof. The monoclonal nanobody and the corresponding NDC can efficiently and high-specifically bind to a purified TF protein and a TF on the surface of various TF abnormally expressed tumor cells, have a high affinity and a low immunogenicity, and have a significant anti-tumor effect in vivo and in vitro.

This invention provides cyclic polypeptide compounds and their uses, specifically disclosing cyclic polypeptide compound A and cyclic polypeptide compound B. Cyclic polypeptide compound A is a compound formed by chelating compound X with a therapeutic radionuclide ion. Cyclic polypeptide compound B is a compound formed by chelating compound X with a diagnostic radionuclide ion. These compounds can be used for the diagnosis and treatment of tumors associated with or mediated by FAP, exhibiting high tumor uptake, long residence times, and broad applicability. JPEG2026513316000414.jpg50104

To provide novel bis-octahydrophenanthrene carboxamides effective for treating diseases and disorders associated with the liver X receptor by forming protein (e.g., antibody) drug conjugates.SOLUTION: The invention provides a compound of Formula I or a pharmaceutically acceptable salt, solvate or stereoisomeric form thereof. (In the formula, Q1 and Q2 are each CH2, C(O), or the like; W is CH2, N(H), or the like; R1 and R2 are each H, OH, or the like; R7 is halogen, C1-6 alkyl, or the like; and n is an integer from 0 to 3.)SELECTED DRAWING: Figure 11

A compound represented by formula (1), or a tautomer, a mesomer, a raceme, an enantiomer, a diastereoisomer thereof, or a mixture form thereof, or a pharmaceutically acceptable salt, a prodrug or a solvate thereof, in which the structure of the formula (1) is as shown in the specification; according to the compound, a strong hydrophilic sulfonic acid inner salt and / or phosphoric acid inner salt side chain is introduced at the position of polypeptide (VC, VA, AAA and the like)-PAB (self-destruction group) of a linker, so that the druggability (including hydrophilicity and stability) of an 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.

The present disclosure provides an antibody-drug conjugate intermediate containing SN38 and a preparation method thereof, comprising introducing a biologically active water-soluble group PEG into its linker and structurally modifying PEG. The preparation method is simple in steps and cost-saving, and does not introduce heavy metal ions in reactions with higher environmental friendliness. Moreover, the antibody-drug conjugate intermediate synthesized by the preparation method has higher stability and efficacy compared with antibody-drug conjugate intermediates with SN38 as toxin in the prior art.

The present disclosure relates to a preparation method of an intermediate of camptothecin derivative. Specifically, the present disclosure relates to a preparation method of a compound as shown in formula (II), which comprises the step of reacting a compound as shown in formula (III) with a compound as shown in formula (VII) in the presence of a base. The method has high yield and mild reaction conditions, and is suitable for industrial production.

To provide a compound, or a related compound, comprising folate as a ligand linked to a steroid via a linker.SOLUTION: A compound of formula (I), or a pharmaceutically acceptable salt, polymorph, prodrug, solvate, or clathrate thereof; a composition comprising such a compound; and the use of such a compound and composition for treating, for example, inflammation associated with a disease or disorder. Formula (I): G1-L-G2, where G1 is a folate radical, an antifolate radical, or a folate analog radical; L is a linker; and G2 is a radical of a steroid.SELECTED DRAWING: None

The invention discloses a camptothecin compound and a conjugate thereof. The invention provides a compound as shown in a formula I, a solvate of the compound, a pharmaceutically acceptable salt of the compound or a solvate of the pharmaceutically acceptable salt of the compound. The camptothecin compound disclosed by the invention has better anti-tumor activity, and the antibody drug conjugate prepared based on the camptothecin compound also has better anti-tumor activity.