50 results about "DDR1" patented technology

The invention discloses an application of a sulfanyl acetamide compound with a structure shown in a formula I in preparation of a medicine for preventing and / or treating tumors and idiopathic pulmonary fibrosis. The compound can be stably combined with key amino acid residues of DDR1 protein, has a remarkable inhibition effect on phosphorylation activation of the DDR1 protein and various tumor cells, plays an anti-tumor role by effectively inhibiting protein activity, and provides an effective lead compound for subsequent drug design. # imgabs0 #

The invention relates to the technical field of radiopharmaceutical labeling, in particular to a compound targeting a DDR1 receptor and a radioactive tracer derived from the compound. According to the present invention, the radioactive tracer agent generated after the mixing reaction of the DDR1 receptor targeting compound and the radionuclide has strong receptor binding force with the DDR1 receptor, can accurately position the DDR1 receptor in vivo, has excellent in-vivo targeting performance, and can achieve the tumor molecular imaging purpose through nuclear medicine imaging. The invention relates to a DDR1 receptor targeting compound, which has a structural formula as shown in a formula (I): # imgabs0 # formula (I).

The invention relates to a USP7-targeted DDR1 protein degradation agent as well as a preparation method and application thereof, in particular to a compound as shown in a formula I in the specification, and discloses a preparation method and application of the compound and a pharmaceutical composition containing the compound. The compound has excellent DDR1 degradation activity and anti-proliferative activity, and can be used for treating cancers and other diseases related to DDR1 activity. # imgabs0 #

Provided are methods and dosage regimens for treating cancer using an antibody that specifically binds to human DDR1.

Provided herein are compounds, such as compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, and compositions, methods, uses, and kits thereof. The compounds provided herein are DDR1, DDR2, or p38 MAPK (e.g., p38-alpha) inhibitors and are therefore useful for the treatment and / or prevention of various diseases and conditions (e.g., inflammatory diseases, joint diseases, proliferative diseases, fibrosis, or pain).

The present invention relates to the technical field of molecular imaging probes, and particularly relates to a molecular imaging probe labeling precursor targeting the DDR1 receptor, a probe thereof, and a preparation method and application thereof. The molecular imaging probe labeling precursor targeting the DDR1 receptor provided by the present invention reacts with a radionuclide to generate a molecular imaging probe targeting the DDR1 receptor, which has a strong receptor binding force with the DDR1 receptor, can accurately locate the DDR1 receptor in vivo, has excellent in vivo targeting performance, and realizes the purpose of tumor molecular imaging through nuclear medicine imaging. Compared with the radioactive tracer [68Ga]Ga-SDUHYX01, the molecular imaging probe [68Ga]Ga-SDUHYX04 optimizes the molecular structure, reduces the lipophilicity, adjusts the metabolic pathway of the molecular imaging probe, thereby making the tumor-to-liver ratio of the molecular imaging probe higher, and also showing excellent imaging effects at 60 minutes.

The invention relates to the field of biological medicine, and discloses a nano antibody aiming at DDR1, and a sequence and application thereof. The system disclosed by the invention reveals a DDR1-mediated immune escape network, and completes complete development work from a single-target antibody to a multifunctional fusion protein. The research and development of the DDR1nb-Fc and the derivative fusion protein DDR1nb-Fc-mCD80 of the DDR1nb-Fc and the derivative fusion protein DDR1nb-Fc-mCD80 of the DDR1nb-Fc provide a novel treatment strategy with high efficiency and safety for intractable tumors with abundant collagen matrixes.

The present application relates to the technical field of chemical pharmaceuticals, and provides a quinazoline derivative, a preparation method therefor, and a use thereof. The quinazoline derivative provided in the present application has a strong effect of targeted inhibition of DDR1 / 2 activity, with kinase inhibition activity against DDR1 / 2 reaching low nanomolar concentrations, and can inhibit the activity of DDR1 / 2 in a dose-dependent manner, some compounds achieving pM-level inhibitory activity against DDR1, and being usable in the preparation of a medicament for treating and / or preventing diseases caused by abnormal DDR1 / 2-related signaling pathways. Among the currently reported DDR-targeting compounds in the literature, the derivative is in a leading position and also has relatively good selectivity. The present application provides a preparation method for the quinazoline derivative having a short synthesis route, safe operation process, and feasibility for scaled-up production.

The present invention provides a compound represented by general formula [1] having DDR1 kinase inhibitory activity, a pharmaceutically acceptable salt thereof, or a solvate thereof (in the formula, R1 represents a hydrogen atom, a halogen atom, or an optionally substituted alkyl group; het is a 5-membered to 10-membered heteroaryl group; l1 is-CO-NH <->, and-CRa is equal to CRb <->; x is C-Rc; r2 is a halogenated alkoxy group with 1 to 6 carbon atoms or a halogenated alkyl group with 1 to 6 carbon atoms; r3 and R4 together with the carbon atoms to which they are bonded form optionally substituted C3-C6 cycloalkyl or optionally substituted heterocycloalkyl). # imgabs0 #

The invention relates to the technical field of molecular imaging probes, in particular to a molecular imaging probe labeling precursor of a targeted DDR1 receptor, a probe and a preparation method and application of the molecular imaging probe labeling precursor. The molecular imaging probe of the targeted DDR1 receptor, which is generated by reaction of the marker precursor of the molecular imaging probe of the targeted DDR1 receptor and radionuclide, has relatively strong receptor binding force with the DDR1 receptor, can accurately position the DDR1 receptor in vivo, has excellent in-vivo targeting performance, and achieves the purpose of tumor molecular imaging through nuclear medicine imaging. Compared with a radioactive tracer agent [68Ga] Ga-SDUHYX01, the molecular imaging probe [68Ga] Ga-SDUHYX04 has the advantages that the lipophilicity is reduced and the metabolic pathway of the molecular imaging probe is adjusted by optimizing the molecular structure, so that the tumor liver ratio of the molecular imaging probe is higher, and meanwhile, the molecular imaging probe can also show an excellent imaging effect within 60 minutes.

The present invention relates to novel compounds and pharmaceutical compositions comprising the same. More specifically, the present invention relates to compounds useful as inhibitors of discoidin domain receptor 1 (DDR1) and discoidin domain receptor 2 (DDR2). The compounds are particularly useful in the treatment of cancer and fibrotic diseases.

Provided herein are compounds, such as compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, and compositions, methods, uses, and kits thereof. The compounds provided herein are DDR1, DDR2, or p38 MAPK (e.g., p38-alpha) inhibitors and are therefore useful for the treatment and / or prevention of various diseases and conditions (e.g., inflammatory diseases, joint diseases, proliferative diseases, fibrosis, or pain).

The present invention relates to novel compounds and pharmaceutical compositions comprising the same. More specifically, the present invention relates to compounds useful as inhibitors of discoidin domain receptor 1 (DDR1) and discoidin domain receptor 2 (DDR2). The compounds are particularly useful in the treatment of cancer and fibrotic diseases.

The invention relates to the technical field of biology and medicine, in particular to a DDR1 specific antibody and application thereof in gastric cancer treatment. The DDR1 specific antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 respectively, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 7 respectively. The invention further relates to application of the DDR1 specific antibody to treatment of gastric cancer.

Provides DDR1 inhibitors [Solution] A compound represented by the following formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof is provided. TIFF2026086800000449.tif65169 In the formula, A is a benzene ring or a nitrogen-containing 6-membered ring, B is a substituted 3- to 8-membered monocyclic nitrogen-containing heterocycle, and Het is a 5- to 10-membered monocyclic or bicyclic heterocycle.

The invention discloses a CAR-T cell based on a secretion enhancement strategy as well as a preparation method and medical application thereof. The constructed asCAR-T cell contains a secretion-enhanced chimeric antigen receptor (asCAR for short) and small interfering nucleic acid of DDR1 protein. The asCAR sequentially comprises a single-chain variable fragment scFv, a hinge region, a transmembrane domain, a costimulatory factor, a signal transduction structural domain CD3 zeta and TNFRSF1B ICD from an extracellular structure to an intracellular structure, wherein the TNFRSF1B ICD is a TRAF2 binding structural domain in a TNFR2 cell; the small interfering nucleic acid of the DDR1 protein comprises shRNA-DDR1 (short hairpin ribonucleic acid) or miRNA-DDR1 (micro ribonucleic acid). After the antigen activates the asCAR-T cells, the ICD of the TNFRSF1B enhances the expression of the PD-1 through the NF-kappa B pathway and releases the extracellular vesicles loaded with the shRNA-DDR1 or the miRNA-DDR1. The extracellular vesicles released by the asCAR-T cells degrade PD-L1 on the surfaces of tumor cells and inhibit DDR1 expression, and the immune infiltration and anti-tumor effects of the asCAR-T cells are enhanced based on the positive feedback loop.

The invention relates to the technical field of biological medicine, in particular to application of TOMM40 in preparation of a medicine for treating breast cancer. The invention finds that TOMM40 overexpression promotes the increase of the content of DDR1 in lipid rafts instead of early-stage endosomes; a co-immunoprecipitation experiment shows that TOMM40 and PHB2 interact with DDR1 and SRC, and DDR1 and SRC also interact with each other; the combination of TOMM40 and PHB2 can promote phosphorylation activation of DDR1, the activated DDR1 further promotes activation of SRC interacting with the activated DDR1, activation of a downstream MAPK signal channel is caused, and meanwhile, the activated DDR1 can directly activate an AKT / mTOR channel; furthermore, the invention finds that the killing ability of tumor cells can be obviously enhanced by further utilizing Flurizoline and DDR1-IN-1 to treat the breast cancer cells, and the method is expected to become a new strategy for breast cancer treatment.

This invention relates to novel compounds and pharmaceutical compositions comprising novel isoquinolone compounds. More specifically, the invention relates to compounds useful as inhibitors of discoidin domain receptor 1 (DDR1) and discoidin domain receptor 2 (DDR2). The compounds are particularly useful in the treatment of cancer and fibrotic diseases.

The present invention relates to the technical field of radioactive drug labeling, and particularly relates to a compound targeting the DDR1 receptor and a radioactive tracer derived therefrom. The radioactive tracer formed by mixing the compound targeting the DDR1 receptor with a radionuclide has a strong receptor binding force with the DDR1 receptor, can accurately locate the DDR1 receptor in vivo, has excellent in vivo targeting performance, and realizes the purpose of tumor molecular imaging through nuclear medicine imaging. The compound targeting the DDR1 receptor has the following structural formula shown in formula (I): Formula (I).

The present disclosure relates to antibodies binding to tumor discoidin domain receptor 1 (DDR1) and the uses of the antibodies in detecting and treating cancer.

The invention relates to screening and application of a nano antibody of a DDR1 antigen. Specifically, the invention relates to a nano antibody aiming at DDR1 or an extracellular domain thereof or an antigen binding fragment thereof, and the amino acid sequence of the nano antibody comprises CDR1 as shown in SEQ ID NO: 1, CDR2 as shown in SEQ ID NO: 2 and CDR3 as shown in SEQ ID NO: 3; the CDR1 is shown as SEQ ID NO: 1, or the CDR1 is shown as SEQ ID NO: 4, the CDR2 is shown as SEQ ID NO: 5, and the CDR3 is shown as SEQ ID NO: 6.

Provided herein are anti-DDR1 antibodies and anti-DDR1 immunoconjugates. Such anti-DDR1 antibodies and anti-DDR1 immunoconjugates can be used for treating cancer.

The instant disclosure provides methods of detecting discoidin domain receptor tyrosine kinase 1 (DDR1) phosphorylation to determine the effectiveness or likely effectiveness of DDR1 antagonistic therapies. The disclosure provides antibodies for use in the treatment of DDR1 related disorders that specifically bind to DDR1. Also provided herein are compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, for detecting phosphorylated DDR1.

The invention relates to the technical field of medicinal chemistry, and particularly discloses an imidazo [1, 2-a] pyrazine derivative as well as a preparation method and application thereof. Imidazo [1, 2-a] pyrazine-alkynyl-benzamide is used as a hinge region binding parent nucleus, a substituted phenyl-2, 6-dioxopiperazine structure is used as a key pharmacophore for specifically recruiting E3 ubiquitin ligase, and alkyl, hydroxyl or methoxyl is introduced to a D1 site of phenyl, so that spatial conformation and electron distribution of molecules are regulated and controlled, and the E3 ubiquitin ligase is specifically recruited. The specific binding affinity with the DDR1 is obviously enhanced; meanwhile, by selecting a polymethylene chain with a proper length as a linker L, the formation efficiency and stability of a target protein-PROTAC-E3 ligase ternary complex are effectively improved, so that the compound can realize efficient degradation of DDR1 protein under nanomolar concentration, and a novel PROTAC molecule with higher clinical conversion value is provided for tumor treatment driven by DDR1.

The present invention provides a compound represented by general formula [1] and having a DDR1 kinase inhibitory activity, a pharmaceutically acceptable salt of the compound, or a solvate of the compound or the pharmaceutically acceptable salt (in the formula, R1 represents a hydrogen atom, a halogen atom, or an optionally substituted alkyl group; Het represents a 5- to 10-membered heteroaryl group; L1 represents -CO-NH- or -CRa=CRb-; X represents C-Rc; R2 represents a C1-C6 haloalkoxy group or a C1-C6 haloalkyl group; R3, R4 and carbon atoms to which these residues are bound together form an optionally substituted C3-C6 cycloalkyl group or an optionally substituted heterocycloalkyl group).

The present invention provides a compound represented by general formula [1] and having a DDR1 kinase inhibitory activity, a pharmaceutically acceptable salt of the compound, or a solvate of the compound or the pharmaceutically acceptable salt (in the formula, R1 represents a hydrogen atom, a halogen atom, or an optionally substituted alkyl group; Het represents a 5- to 10-membered heteroaryl group; L1 represents -CO-NH- or -CRa=CRb-; X represents C-Rc; R2 represents a C1-C6 haloalkoxy group or a C1-C6 haloalkyl group; R3, R4 and carbon atoms to which these residues are bound together form an optionally substituted C3-C6 cycloalkyl group or an optionally substituted heterocycloalkyl group).

The invention provides an aryl-substituted DDR1 degradation agent as well as a pharmaceutical composition, a preparation method and application of the aryl-substituted DDR1 degradation agent. Specifically, the invention provides a DDR1 degradation agent with a structure as shown in a formula (I), and the compound is a protein kinase degradation agent and can efficiently and selectively degrade DDR1 protein and inhibit proliferation, migration and invasion of various tumor cells. # imgabs0 #

This invention relates to novel compounds and pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as inhibitors of discoidin domain receptor 1 (DDR1) and discoidin domain receptor 2 (DDR2). The compounds are particularly useful in the treatment of cancer and fibrotic diseases.