912 results about "Kinase protein" patented technology

The present invention discloses substituted 2-amino-9-(3,3-difluoropiperidin-4-yl)-7,9-dihydro-8H-purin-8-one compounds compounds having the structural formula represented by formula (I)： The substituted 2-amino-9-(3,3-difluoropiperidin-4-yl)-7,9-dihydro-8H-purin-8-one compounds, derivatives and pharmaceutically acceptable salts thereof of the present invention are capable of acting as a drug characteristic of a protein kinase inhibitor, in particular for the expression of a protein through a DNA-dependent protein kinase (DNA-PK) and can be used to treat or prevent disorders associated with abnormal protein kinase activity, such as cancer, cancer with brain metastases, cancer with meningeal metastases, glioma, glioblastoma, DIPG, and the like either as monotherapy or combination with other treatments, such as radiation therapy or chemotherapy.

The invention provides compounds of formula (I), or pharmaceutically acceptable salts and pharmaceutical compositions thereof, (I) which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of c-kit or c-kit, CSF1R and PDGFR (PDGFRα, PDGFRβ) kinases.

The disclosure relates to compositions and methods for modulating, e.g., reducing or eliminating, the expression of mutated DMPK via delivery using an adeno-associated viral (AAV) capsid variant. The compositions and methods of the present disclosure are useful in the treatment of subjects who have, have been diagnosed with having, or are at risk of having myotonic dystrophy type 1 or another DMPK-related disorder.

Methods and systems for inducing apoptosis of adipose cells are disclosed herein. In some embodiments, the method comprises identifying a target area comprising the adipose cells and injecting a therapeutic agent at the target area. Injecting the therapeutic agent can inhibit a protein kinase B (Akt) pathway of the adipose cell, induce a proinflammatory response of adipose cells at the target area, and / or initiate lipolysis / cell death of the adipose cells at the target area. In doing so, a volume of the adipose cells at the target area can be reduced.

The present disclosure is directed to DNA-PK inhibitors having the Formula (I), (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, methods of preparing the foregoing, and compositions thereof, as well as methods of use for the compounds of Formula (I), in combination with a DNA cutting agent.

The present disclosure relates to compounds that elicit degradation of proteins directed against the protooncogene tyrosine protein kinase receptor (RET), which may be a wild-type RET or a mutant form of RET, including compounds of formula (I), for use in the treatment of diseases and conditions mediated by said proteins. # imgabs0 #

Methods and systems for inducing apoptosis of adipose cells are disclosed herein. In some embodiments, the method comprises identifying a target area comprising the adipose cells and injecting a therapeutic agent at the target area. Injecting the therapeutic agent can inhibit a protein kinase B (Akt) pathway of the adipose cell, induce a proinflammatory response of adipose cells at the target area, and / or initiate lipolysis / cell death of the adipose cells at the target area. In doing so, a volume of the adipose cells at the target area can be reduced.

The present disclosure is directed to DNA-PK inhibitors having the Formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, methods of preparing the forgoing, and compositions thereof, as well as methods of use for the compounds of Formula (I), in combination with a DNA cutting agent.

The invention provides a synthetic anti-cancer lipopeptide and application thereof, and particularly provides a non-natural polypeptide comprising domains X1, X2 and X3, in which X1 is selected from C6-C20 fatty acid residues, X2 is selected from C6-C20 fatty acid residues, X3 is selected from C6-C20 fatty acid residues, and X3 is selected from C6-C20 fatty acid residues; x2 is selected from a fragment of a cell penetrating peptide (CPPs); x3 is selected from fragments of peptides that specifically bind to protein kinase 2 (CK2). Compared with the prior art, the polypeptide can more effectively inhibit CK2, has higher targeting property on RPS6 protein, has better tumor inhibition activity and anti-metastasis effect and higher safety, and can realize large-scale production.

The invention discloses a receptor-like protein kinase gene containing a Malectin-like structural domain and associated with the heat resistance character of cotton, and belongs to the field of biotechnology application. The invention provides a cDNA (complementary deoxyribonucleic acid) sequence (SEQ ID NO.1) and a genomic sequence (SEQ ID NO.2) of the gene in allotetraploid upland cotton, 456 upland cotton varieties can be divided into two haplotype promoters according to a heat-resistant character GWAS associated site A11: 20036111, the sequence of a CC heat-labile haplotype promoter is shown as SEQ ID NO.3, and the sequence of a TT heat-resistant haplotype promoter is shown as SEQ ID NO.4. The invention also provides a method for preparing the promoter. The gene provided by the invention is obtained by cotton variety re-sequencing and whole genome association analysis, and is significantly associated with the heat-resistant character of cotton, and two promoter haplotypes of the gene are utilized to distinguish heat-resistant and non-heat-resistant haplotypes. The gene has important research value and application prospect in improvement of the heat-resistant character of cotton and cultivation of new heat-resistant varieties of cotton.

The present disclosure is directed to DNA-PK inhibitors having the Formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, methods of preparing the forgoing, and compositions thereof, as well as methods of use for the compounds of Formula (I), in combination with a DNA cutting agent.

Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure provides methods of inhibiting RAN protein translation by contacting a cell with an effective amount of an inhibitor of eIF2 phosphorylation or an inhibitor of protein kinase R (PKR). In some embodiments, methods described by the disclosure are useful for treating diseases associated with RAN protein translation, such as certain neurodegenerative diseases.

The invention discloses an application of a Piezo1 inhibitor in preparation of a medicine for treating necrotizing enterocolitis. The Piezo1 inhibitor can be applied in preparation of the medicine for treating the necrotizing enterocolitis. The Piezo1 inhibitor can also be applied to preparation of drugs for relieving NEC intestinal epithelial barrier injury. The Piezo1 inhibitor can also be applied to preparation of drugs for reducing calcium influx in intestinal epithelial cells and calcium / calmodulin dependent protein kinase activity. The application has the beneficial effects that the effect and mechanism of the Piezo1 for regulating and controlling the calcium ion influx and promoting the NEC severity degree by the calcium / calmodulin dependent protein kinase activity level are discussed for the first time from multiple aspects of animals, tissues, cells, molecules and the like, and the effect and mechanism of the activated intestinal epithelial cell Piezo1 in NEC inflammatory injury and barrier repair are clarified for the first time; the knockout of the gene can improve the NEC severity of mice, and a new intervention target is provided for clinical treatment.

The invention belongs to the technical field of plant heredity and genetic engineering, and particularly relates to a wheat saline-alkaline tolerant protein kinase gene TaCRCK and application thereof. Specifically, the invention discloses a wheat saline-alkaline tolerant protein kinase gene TaCRCK, and the nucleotide sequence of cDNA of the gene is as shown in SEQ ID NO. 1. The invention also discloses a plant expression vector containing the gene TaCRCK and application of the gene and the plant expression vector in cultivation of saline-alkali resistant plants. Tests prove that silent expression of the gene promotes the resistance of wheat to saline-alkaline stress, and the saline-alkaline tolerance of transgenic plants is obviously improved. The gene has a negative regulation effect on the salt and alkali tolerance of plants, provides a new tool and method for improving the salt tolerance of crops by using a genetic engineering means, and has important scientific significance and application prospects.

The invention relates to application of mitogen-activated protein kinase PiPmk1 in screening molecules for inhibiting formation of a phytophthora infestans infection structure. The invention finds that the molecular marker plays a key role in the development of a phytophthora infestans cyst bud tube and / or the formation of an infection structure, which indicates that the molecular marker has the potential of serving as a target for inhibiting phytophthora infestans infection, and a corresponding molecular screening method and a generative prediction model are further developed and utilized; rapid and accurate prediction and screening of phytophthora infestans infection inhibitory molecules are realized, the research and development period and cost are greatly shortened, and a new thought and a new method are provided for development of accurate targeted green pesticides.

The invention discloses injectable piezoelectric conductive hydrogel as well as a preparation method and application thereof, and the injectable piezoelectric conductive hydrogel is prepared by forming space coordination between piezoelectric nano-particles and conductive hydrogel through metal and a framework and uniformly fixing the piezoelectric nano-particles in the space structure of the conductive hydrogel. When the injectable piezoelectric conductive hydrogel is injected to the wound surface of a mouse wound, the hydrogel can be completely attached to the wound according to the irregular wound to form gel, and the gel is tightly attached to the wound. When a mouse moves, the piezoelectric nanoparticles are extruded to generate voltage and current, and the current is transmitted to the surface and wound of the hydrogel through the conductive hydrogel skeleton. Under the stimulation of micro-current, phosphorylation of phosphatidylinositol 3-kinase of fibroblasts is activated, then phosphorylation of protein kinase B is activated, migration and proliferation of the fibroblasts are induced, and wound healing is promoted.

The invention belongs to the technical field of biological medicines, and particularly discloses application of (E)-BCI hydrochloride in preparation of a medicine for treating sepsis. According to the application of the (E)-BCI hydrochloride in preparation of the medicine for treating sepsis, by inhibiting the activity of bispecific phosphatase 6, a mitogen activated protein kinase signal channel is regulated and controlled, and the expression level of inflammatory factors IL-1beta and TNF-alpha is reduced. The invention discloses application of (E)-BCI hydrochloride in preparation of drugs for treating sepsis, BCI enters from a new target for regulating inflammation and immune balance through a targeted DUSP6 / MAPK signal channel, a non-antibiotic-dependent drug is provided for treatment of sepsis, and the (E)-BCI hydrochloride is especially suitable for systemic inflammatory response syndromes caused by infection, operations, wounds and other inducements, and has a wide application prospect. Wide clinical application prospects are realized.

The invention relates to the technical field of drugs for gene therapy, in particular to application of CAP-Gly functional peptide in preparation of drugs for treating fatty liver. The invention provides application of a CAP-Gly functional peptide or a reagent for improving the expression quantity of the CAP-Gly functional peptide in preparation of a medicine for treating fatty liver. The amino acid sequence of the CAP-Gly functional peptide is shown as SEQ ID NO.23. The invention further provides a preparation method of the CAP-Gly functional peptide. The invention finds that the overexpression of the KIF13B protein or the CAP-Gly functional peptide thereof in mice can effectively reduce lipid accumulation in liver cells and increase phosphorylation of protein kinase alpha activated by adenosine monophosphate, and provides a new target and a new strategy for precise treatment of patients with fatty liver (especially metabolism-related fatty liver diseases) clinically.

The invention belongs to the field of plant genetic engineering, and discloses a key gene OsHPCA1 for positively regulating salt stress and oxidative stress tolerance of rice. The gene (with the login number of Os05g40770) encodes a receptor protein capable of specifically sensing hydrogen peroxide, and belongs to a leucine repeat receptor-like protein kinase (LRR-RLKs) family, wherein the family is the largest subfamily in the receptor-like protein kinase (RLKs). The OsHPCA1 responds to salt and oxidative stress signals, and the salt tolerance and oxidative stress resistance of the rice are positively regulated and responded. The OsHPCA1 overexpression rice strain shows very strong salt tolerance; and the OsHPCA1 knockout strain oshpca1 is more sensitive to salt stress. The OsHPCA1 protein encoded by the OsHPCA1 gene and rich in leucine repeat receptor-like protein kinase can positively regulate and control the activity of catalase C (CatC) in rice and enhance the removal efficiency of H2O2 under salt stress, so that the salt tolerance of rice is improved. When the OsHPCA1 is overexpressed, the activity of CatC in the overexpressed strain OsHPCA1 is obviously increased, the H2O2 removal capability is enhanced, and the salt tolerance and oxidative stress tolerance of the rice are improved.

A compound for degrading a Wee1 protein kinase or a pharmaceutically acceptable salt thereof, and the use thereof in the treatment of proliferative diseases.

The present invention relates to compounds of formula (I) below, or any one of its pharmaceutically acceptable salts: [Formula 1] JPEG2023523788000127.jpg41170 where R 1 is (C1-C6) alkyl group, spiro (C5-C 11 ) bicyclic rings, fused phenyl groups, substituted phenyl groups, R'-L- groups, where L is either a single bond or a (C1-C3) alkanediyl group, and R' is a (C3-C8) cycloalkyl group, a bridged (C6-C 10 ) cycloalkyl group, (C3-C8) heterocycloalkyl group, or (C3-C8) heteroaryl group, or R'-L- group, where L is a (C1-C3) alkanediyl group and R' is an optionally substituted phenyl group, and R 2 represents a hydrogen atom or a (C1-C3) alkyl group. The present invention further relates to compositions comprising the compound of formula (I), as well as methods for preparing the compound and synthetic intermediates thereof. The present invention also relates to the compound for use as a pharmaceutical, in particular for treating and / or preventing cognitive impairment associated with Down's syndrome; Alzheimer's disease; dementia; tauopathies; Parkinson's disease; CDKL5 deficiency disorders; Phelan-McDermid syndrome; autism; type 1 and type 2 diabetes; folate and methionine metabolism disorders; osteoarthritis; Duchenne muscular dystrophy; some cancers; neuroinflammation, anemia, and viral and unicellular infections, and for regulating body temperature.

Disclosed are a series of isoquinolone derivatives as ROCK protein kinase inhibitors and uses thereof in preparing medicaments for ROCK protein kinase inhibitor-related glaucoma or ocular hypertension diseases. Specially, disclosed are a compound of formula (I), an isomer thereof or a pharmaceutically acceptable salt thereof.

Compounds that inhibit p38α MAPK protein, and methods of using the same, are provided for treating or preventing diseases such as cancer or inflammatory diseases.

Provided herein are compositions and methods for producing milk proteins, which allow for safe, sustainable and humane production of milk proteins for commercial use, such as use in food compositions. The disclosure provides recombinant fusion proteins comprising at least first protein and a second protein, wherein at least one of the first protein and the second protein is a milk protein, or fragment thereof. The disclosure also provides methods for producing the recombinant fusions proteins, and food compositions comprising the same.

The present application relates to a proteolysis targeting chimera compound represented by formula (A) for degrading IRAK4 and a preparation method therefor, a pharmaceutical composition comprising said compound, and a use of the pharmaceutical composition for treating diseases, disorders or conditions associated with the kinase protein IRAK4.

The invention provides compounds of formula (I), or pharmaceutically acceptable salts and pharmaceutical compositions thereof,which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of c-kit or c-kit, CSF1R and PDGFR (PDGFRα, PDGFRβ) kinases.

Described is a combination of a prophylactic or therapeutic agent for glaucoma or ocular hypertension, which is useful as a prophylactic or therapeutic agent for glaucoma or ocular hypertension. By combining sepetaprost and a Rho-associated coiled-coil containing protein kinase inhibitor(s), an intraocular pressure lowering action is enhanced as compared with the case where each drug is used alone. As the form of administration, they may be administered concomitantly or may be administered as a combination drug.

The present disclosure provides anti-tyrosine-protein kinase membrane receptor 1 antibody-drug conjugate structures. The antibody-drug conjugate structures include a branched linker, where two or more payloads per branched linker are attached to an antibody. In addition, the disclosure also encompasses compounds and methods for production of such conjugates. In addition, the disclosure also encompasses methods of using the conjugates.

The invention relates to RIP1 inhibiting compounds and methods of making and using the same. In particular, disclosed herein are kinase inhibitory compounds, such as receptor interacting protein-1 (RIP1) kinase inhibitor compounds, and pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions and / or combinations may be used to treat or prevent kinase-related diseases or disorders, particularly RIP1-related diseases or disorders.