81 results about "RIPK1" patented technology

This invention relates to the field of pharmaceutical technology, specifically to a substituted pyridotriazole compound, its preparation method, and its uses. This specification discloses a substituted pyridotriazole compound that inhibits RIPK1 and / or MLK, as well as its pharmaceutically acceptable salts, stereoisomers, solvent compounds, or prodrugs. The compound is shown in formula (I), where the definitions of each group are detailed in the specification. Furthermore, this invention also discloses pharmaceutical compositions comprising this compound and their use in the preparation of medicaments for treating RIPK1-related diseases or conditions.

The present invention provides a polycyclic compound, a pharmaceutical composition thereof, and a use thereof. The polycyclic compound of the present invention has a structure as shown in formula A, wherein the definitions of R1-R6, ring A-ring E, L, n, m, q, and t are as described herein. The compound of the present application is an RIPK1 inhibitor, which can be used for treating an RIPK1-related disease.

The invention relates to a method for screening a medicine for treating tumors by using a target spot. The method comprises the following steps: determining whether a to-be-detected medicine is combined with the RIPK1 protein serving as the target protein or not, and if the to-be-detected medicine is combined with the target protein, testing the inhibitory activity of the to-be-detected medicine on the survival and / or growth of tumor cells. Therefore, the period of screening target spots and candidate drugs with clear anti-tumor mechanisms can be obviously shortened, and a new way and a new method are provided for treating tumors, especially drug-resistant tumors, by taking the RIPK1 as the target spot.

The invention provides a method for treating autoimmune diseases mediated by regulatory T cell (Treg) programmed necrosis. Specifically, the invention provides application of an O-linked beta-N-acetylglucosamine glycosylation (O-GlcNAcylation) accelerant, and the O-linked beta-N-acetylglucosamine glycosylation accelerant is used for preparing a medicine or a preparation for treating programmed necrosis type autoimmune diseases. It is found for the first time that when the O-GlcNAcylation promoter is used for improving the O-GlcNAcylation level of RIPK1 / 3 protein, Treg programmed necrosis can be effectively inhibited, and therefore autoimmune diseases are improved.

The invention provides an application of OGA as an inhibition target in preparation of drugs for treating GBC, and relates to the technical field of biomedicine.According to a specific verification test, it is found that GBC cells transfer OGA to neurons through EVs, so that glycosylation of RIPK1 is inhibited, phosphorylation and activation of RIPK1 are promoted, and finally neuronal necroptosis is induced. RIPK1 is a core factor for regulating and controlling cell survival, inflammatory response and programmed death, and is activated through a compound IIb pathway under the action of exogenous OGA. EV-induced invasion and necroptosis can be remarkably inhibited through neuron OGA knock-down, so that the aim of treating GBC is achieved.

The present disclosure provides a compound of formula (I), a pharmaceutical composition thereof, and a use thereof in treating and / or preventing diseases or conditions related to the activity of RIPK1 kinase.

The present invention relates to compounds of formula (I), pharmaceutical compositions containing them, processes for their preparation, and their use as receptor interacting protein kinase 1 (RIPK1) inhibitors. The invention also relates to application of the compound or the composition containing the compound to treatment or prevention of related diseases or symptoms mediated by RIPK1. # imgabs0 #

The present invention relates to heterocyclic compounds, pharmaceutical compositions containing the same, processes for their preparation, and their use as RIPK1 inhibitors. The compound is a compound as shown in formula (I), or an isomer, a prodrug, a solvate, a stable isotope derivative or a pharmaceutically acceptable salt thereof. The invention also relates to the use of said compounds for the treatment or prevention of related diseases and dysfunctions mediated by RIPK1 and to methods of using the same to treat said diseases. # imgabs0 #

Disclosed in the present invention are six-membered-ring and five-membered N-heterocycle fused amide compounds and the use thereof, belonging to the technical fields of chemical and medicine. The six-membered-ring and five-membered N-heterocycle fused amide compounds shown as formula (I) provided by the present invention can target the RIPK1 enzyme, have the advantages of high activity and high selectivity, and also have excellent pharmacokinetic properties.

The present invention pertains to the treatment of diseases associated with a dysregulated immune response such as auto immune disorders, inflammatory diseases or pathological immune responses as adverse effects of medical treatments. In particular the invention provides a combined use of inhibitors of Receptor-interacting serine / threonine-protein kinase (RIPK1) and inhibitors of Inhibitor of κB (IκB) Kinase (IKK) in subjects suffering from such disorders. The invention provides such inhibitory compounds and their combinations for use in medical applications, as well as pharmaceutical compositions comprising the compounds of the invention.

The invention relates to a tetrahydrocyclopentapyrazole compound which simultaneously has RIPK1 inhibitory activity, free radical scavenging capacity and lipid peroxidation resistance, and application of the tetrahydrocyclopentapyrazole compound in preparation of drugs for treating or preventing RIPK1-mediated diseases or diseases caused by programmed necrosis of cells. Specifically, the invention relates to a compound as shown in a general formula, and pharmaceutically acceptable salt or stereoisomer thereof.

The invention provides novel substituted heterocyclic compounds represented by Formula I, or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of RIPK1 and the therapeutic methods.

The present application provides an application of an RIPK1 O-GlcNAc glycosylation inhibitor in the preparation of a drug for enhancing the sensitivity of sunitinib to renal cell carcinoma. The present application discovers that RIPK1 O-GlcNAc glycosylation, especially the O-GlcNAc glycosylation of serine at positions 331, 440, and 669, reduces the sensitivity of renal cell carcinoma to sunitinib. Therefore, by inhibiting RIPK1 O-GlcNAc glycosylation or knocking down the expression of O-GlcNAc transferase, the sensitivity of renal cell carcinoma to sunitinib can be increased. Therefore, the O-GlcNAc glycosylation level of RIPK1 can be used as a biomarker for predicting the sensitivity of renal cell carcinoma to sunitinib; by using an RIPK1 O-GlcNAc glycosylation inhibitor to reduce the RIPK1 O-GlcNAc glycosylation level, especially the O-GlcNAc glycosylation of serine at positions 331, 440, and 669, the sensitivity of renal cell carcinoma to sunitinib can be increased, and the therapeutic effect of sunitinib can be improved.

The present disclosure relates to a fused heterocyclic compound, and a preparation method therefor and a medical use thereof. Specifically, the present disclosure relates to a fused heterocyclic compound shown in general formula (I), a preparation method for the compound, a pharmaceutical composition containing the compound, and a use of the compound as an RIPK1 kinase inhibitor, in particular a use in the preparation of a drug for treating and / or preventing RIPK1 kinase-mediated diseases or conditions.

Protein phosphatase 5 (PP5) is a serine / threonine protein phosphatase involved in the maturation and activation of numerous signaling pathways essential for cancer growth. PP5 activity is essential for the survival of clear cell renal cell carcinoma (ccRCC), however the mechanism remains unclear. Data demonstrates that PP5 interacts with caspase-8, FADD, and RIPK1, components of extrinsic apoptotic pathway Complex II. Specifically, PP5 dephosphorylates and inactivates the death effector proteins RIPK1 and FADD, preserving Complex II integrity and regulating extrinsic apoptosis. Protein phosphatases are considered to be ‘undruggable,’ however we have developed a specific inhibitor of PP5 (P-053) that prevents substrate binding to the active site. Encouragingly, PP5 inhibition using P-53 in VHL-null ccRCC robustly induces extrinsic apoptosis. Taken together, the data suggests that PP5 promotes ccRCC survival by suppressing extrinsic apoptosis, and small molecule inhibition of PP5 presents a viable therapeutic strategy for ccRCC.

The present invention relates to a compound of formula (I), a pharmaceutical composition containing same, a preparation method therefor, and a use thereof as a receptor-interacting protein kinase 1 (RIPK1) inhibitor. The present invention further relates to a use of the compound or composition containing same for treatment or prevention of related diseases or disorders mediated by RIPK1.

The present disclosure provides a compound of formula (I), a pharmaceutical composition thereof, and a use thereof in treating and / or preventing diseases or conditions related to the activity of RIPK1 kinase.

Provided is an RIPK1 inhibitor, which is a compound as shown in formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, metabolite or prodrug thereof. Also provided are a method and a use of the RIPK1 inhibitor in treatment and / or prevention of diseases or symptoms related to abnormal RIPK1 activity, or mediated by RIPK1.

The present invention relates to benzoxazepine compounds, pharmaceutical compositions containing the same, processes for their preparation, and their use as RIPK1 inhibitors. The compound is a compound as shown in formula (I), or an isomer, a prodrug, a solvate, a stable isotope derivative or a pharmaceutically acceptable salt thereof. The invention also relates to the use of said compounds for the treatment or prevention of related diseases and dysfunctions mediated by RIPK1 and to methods of using the same to treat said diseases. # imgabs0 #

The invention discloses a bicyclic compound and an application of the bicyclic compound in a medicine, and particularly relates to a novel bicyclic compound and a medicine composition containing the novel bicyclic compound. The invention also relates to a method for preparing the compound, and application of the compound or the pharmaceutical composition in preparation of drugs for treating RIPK1 inhibitor mediated diseases and / or symptoms. The invention relates to the field of medicines, in particular to the application of the medicines in preparing medicines for treating diseases such as idiopathic pulmonary fibrosis, graft versus host disease, ulcerative colitis, rheumatoid arthritis, multiple sclerosis, amyotrophic lateral sclerosis, systemic inflammatory response syndrome, lupus erythematosus, Alzheimer's disease, psoriasis, non-alcoholic steatohepatitis, osteoarthritis and the like.

This disclosure relates to formula (I) [Formula 1] TIFF2026520851000227.tif38170 (wherein R1 represents a phenyl or monocyclic heteroaryl optionally substituted by 1, 2, or 3 R3s, R2 represents an aryl or heteroaryl optionally substituted by 1, 2, or 3 R6s, each R3 independently selected from halogens, cyanos, (C1-C4)alkyl groups, or (C1-C4)alkoxy groups, R4 and R5 independently selected from halogens, (C1-C4)alkyl groups, or (C1-C4)alkoxy groups, or R4 and R5 together form a (C1-C4)alkylene bridge, and m and s are independently (The values ​​are 0 or 1, p, q, r and t are independently 0 or 1, and each R6 is independently selected from halogen, cyano, -NH2 group, -OH, (C1~C4)alkyl group, -CF3, -C(O)NH2, -C(O)NH-(C1~C4)alkyl group, -C(O)OH, -C(O)O-(C1~C4)alkyl group, -SO2NH2, (C1~C4)alkoxy group, -O-(C1~C4)alkylene-(C3~C6)cycloalkyl group, -O-(C3~C6)cycloalkyl group, -O-(C3~C6)heterocycloalkyl group, (C3~C6)heterocycloalkyl group, heteroaryl group and oxo) This disclosure relates to the compound or its pharmaceutically acceptable salts, solvates, or stereoisomers. The disclosure further relates to pharmaceutical compositions containing the novel compound.

The invention relates to an RIPK1 inhibitor, which is a compound as shown in a formula (I), or a pharmaceutically acceptable salt, a stereoisomer, a solvate, a polymorphic substance, a metabolite or a prodrug thereof. The present application also relates to methods and uses of the RIPK1 inhibitors in the treatment and / or prevention of diseases or symptoms associated with abnormal RIPK1 activity, or mediated by RIPK1.

The invention discloses a small molecular compound targeting ZBP1 and application thereof, and belongs to the technical field of biological medicine. The small molecule compound targeting ZBP1 is 9 ''-salvianolic acid B monomethyl ester, the CAS number is 1167424-31-8, experiments verify that the 9''-salvianolic acid B monomethyl ester is combined with an RHIM structural domain of ZBP1, combination of ZBP1 with RIPK1 and RIPK3 is inhibited, and therefore downstream pathway activation is inhibited, and therefore the ZBP1 targeting inhibitor is provided and used for preparing a medicine for treating diseases caused by excessive activation of ZBP1, and the application prospect is wide. Such as autoinflammatory diseases, tissue damage and chronic inflammatory diseases. A small molecule compound 9 ''-salvianolic acid B monomethyl ester capable of being combined with ZBP1 is screened from an existing small molecule compound library, the effectiveness of targeted inhibition of ZBP1 expression is proved through experiments, and a new thought is provided for treating diseases caused by excessive activation of ZBP1.

The present application relates to the application of Necrostatin-1 in the preparation of a drug for preventing and / or treating acute aristolochic acid nephropathy. The typical pathological change of acute aristolochic acid nephropathy is the necrosis of renal tubular epithelial cells, and Necrostatin-1 can target this change to prevent and / or treat acute aristolochic acid nephropathy. Necrostatin-1 can significantly inhibit the kinase activity of RIPK1, block the endogenous and exogenous apoptosis pathways dependent on RIPK1, delay the apoptosis and GSDME-dependent pyroptosis of renal tubular epithelial cells, effectively improve the damage of renal tubular epithelial cells, and achieve the purpose of treating acute aristolochic acid nephropathy. The present application can provide a new strategy for the treatment of acute aristolochic acid nephropathy. Necrostatin-1 can be widely used in the preparation of drugs for treating acute aristolochic acid nephropathy.