109 results about "RIPK1" patented technology

The present invention provides a class of programmed cell death inhibitors, a preparation method therefor and a use thereof. Specifically, the present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, the compound being as shown in Formula I. The present invention also provides a method for preparing the compound and a pharmaceutical composition comprising the compound or a use thereof in treating or preventing diseases or conditions associated with programmed cell death and / or human receptor-interacting protein 1 kinase (RIPK1).

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 crystalline compound of the formula:wherein the crystalline compound is useful for treating autoimmune and inflammatory diseases, such as atopic dermatitis, rheumatoid arthritis, and psoriasis.

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 discloses a benzo-aza # imgabs0 # ketone derivative, and particularly relates to substance forms such as free alkali, an isomer or pharmaceutically acceptable salt of the derivative. Furthermore, the invention also discloses a preparation method and pharmaceutical application of the benzaza # imgabs1 # ketone derivative, and the benzaza # imgabs1 # ketone derivative can be used as an RIPK1 inhibitor for treating diseases related to abnormal expression of a mediated RIPK1 signal channel, including but not limited to tumors, and has great clinical development value.

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 invention provides a programmed cell necrosis inhibitor as well as a preparation method and application thereof. Specifically, the invention provides a compound, or pharmaceutically acceptable salts, hydrates or solvates thereof, and the compound is as shown in a formula I in the specification. The invention also provides a preparation method of the compound and a pharmaceutical composition containing the compound or application of the compound in treatment or prevention of programmed necrosis of cells and / or human receptor interacting protein 1 kinase (RIPK1) related diseases or symptoms. # imgabs0 #

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 invention provides novel substituted heterocyclic rings 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 invention discloses an inhibitor targeting RIPK1 kinase and application of the inhibitor. The inhibitor targeting RIPK1 kinase is selected from a compound with a structure shown in a general formula (I) or pharmaceutically acceptable salt of the compound. The invention provides a series of novel kinase targeted inhibitors, and the compound disclosed by the invention can effectively target RIPK1 kinase and can be used as an effective therapeutic agent for inflammation-related diseases. # imgabs0 #

The present invention discloses a RIPK1 inhibitor for inhibiting programmed cell necrosis and a preparation method thereof. The RIPK1 inhibitor of the present invention is shown in general formula I, wherein X 1 , X 2 , X 3 , X 4 , X 5 , Z 1 , Z 2 , Z 3 , L 1 , L 2 , L 3 , R, R 1 , ring D and n are as shown in the specification and claims. The present invention also discloses a preparation method of the general formula I and its activity test results of inhibiting programmed cell necrosis and RIPK1. The general formula I compound of the present invention can be used to prepare drugs for treating and preventing inflammatory and degenerative diseases.

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.