104 results about "Kinase activity" patented technology

The present disclosure provides compounds of formula (I), pharmaceutical compositions thereof, and uses thereof in the treatment and / or prevention of diseases or conditions associated with CDK9 kinase activity. JPEG2025538275000286.jpg3450

The present invention belongs to the field of medical technology and specifically disclosed is a compound represented by formula (I′), or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, and each symbol therein is as defined in the claims. The compound of the present invention may be used as a drug for regulating RET kinase activity or treating RET-related diseases, and has better pharmacokinetic properties.

Compounds and salts thereof that are useful as JAK kinase inhibitors are described herein. Also provided are pharmaceutical compositions that include such a JAK inhibitor and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a Janus kinase activity in a patient.

The invention relates to the technical field of compound synthesis, in particular to an aminopyrimidine compound, a pharmaceutical composition, application of the aminopyrimidine compound and an intermediate compound. The structural formula of the aminopyrimidine compound is shown as a formula (I), and the aminopyrimidine compound can effectively inhibit the activity of NUAKs kinase, and especially has a good inhibition effect on the activity of NUAK1 kinase and the activity of NNUAK2 kinase. Formula (I).

The application discloses application of 12-ketolithocholic acid in preparation of a medicine for preventing or treating atopic dermatitis, and the 12-ketolithocholic acid can inhibit NUAK2 kinase activity expression and activity, and then negatively regulates a downstream TNF inflammatory signal path, significantly down-regulates IL-1beta, IL-8 and various proinflammatory factor secretion, and inhibits keratinocyte excessive inflammatory activation. The 12-ketolithocholic acid and ginsenoside F2 are compounded and used in combination to produce synergistic effect, and the anti-inflammatory effect is further enhanced; the active substance has low cytotoxicity and good safety, can be prepared into an external ointment or an oral preparation, and has a wide application prospect in the field of atopic dermatitis prevention and treatment.

The present application relates to the field of biological medicine and modernization of traditional Chinese medicine, and particularly relates to a therapeutic target, an inhibitor and a traditional Chinese medicine composition for treating ovarian hypofunction caused by oxidative stress and application thereof. The present application first determines SRC tyrosine kinase as a key drug target for preventing and treating the disease. The application of the SRC tyrosine kinase inhibitor (such as secaitinib) in preparing related drugs is provided, which can alleviate the damage of ovarian granulosa cells by inhibiting the SRC activity, down-regulating the expression of antioxidant enzyme related genes and reducing the level of active oxygen. Meanwhile, the present application provides a traditional Chinese medicine composition composed of mulberry, kudzu root, tuckahoe and medlar. The composition can improve the hormone level, enhance the antioxidant capacity, improve the ovarian function and fertility by inhibiting the SRC tyrosine kinase activity and the SRC-RAF1-MEK-ERK signal pathway. The present application provides a new solution for the targeted treatment of ovarian hypofunction and the modernization of traditional Chinese medicine.

The invention belongs to the technical field of biological medicines, and particularly relates to application of dirithromycin in preparation of a product for treating LINC00516 high-expression lung adenocarcinoma. The invention discloses the effect of the long-chain non-coding RNA LINC00516 in abnormal activation of the lung adenocarcinoma cell cycle for the first time. Researches show that LINC00516 is directly combined with CDK1, the kinase activity of CDK1 is remarkably enhanced, and the inhibitory phosphorylation level of CDK1 is reduced, so that lung adenocarcinoma cells are driven to quickly enter a G2 / M phase, and tumor cell proliferation is accelerated. The invention further innovatively proposes that dirithromycin is used as an intervention means, and by blocking the combination of LINC00516 and CDK1, the activity of CDK1 is effectively reduced, and the proliferation capacity of tumor cells is inhibited. In-vivo and in-vitro experiments prove that the dirithromycin can obviously inhibit the growth of lung adenocarcinoma cells with high expression of LINC00516, so that a brand-new molecular targeting treatment strategy is provided for clinic.

In one aspect, a novel method that allows for evaluation of an RTK activity is provided. Provided is a method for evaluating an RTK activity, the method including: a step (A1) for determining diffusion dynamics A1 of the RTK by contacting a target substance with a cell that expresses a labeled RTK on a cell membrane, a step (B1) for determining diffusion dynamics B1 of the RTK by contacting the target substance and a ligand that activates the RTK with the cell that expresses the labeled RTK on a cell membrane, a step (C1) for calculating a ratio of the diffusion dynamics A1 of the RTK obtained at the step (A1) and the diffusion dynamics B1 of the RTK obtained at the step (B1), and a step (D1) for evaluating an effect of the target substance on an RTK activity by comparing the ratio of the diffusion dynamics obtained at the step (C1) with a threshold; and at the step (D1), when the ratio of the diffusion dynamics obtained at the step (C1) is equal to or greater than the threshold, it can indicate that the target substance has an effect on a molecular function of the RTK.

The invention provides novel compounds, pharmaceutical compositions, and their use for inhibiting c-kit kinase activity.

The invention provides natto as well as a preparation method, health-care food and application thereof. The preparation method comprises the following steps: soaking soybeans; sterilizing the soaked soybeans; inoculating the sterilized soybeans with bacillus natto for first-stage fermentation, and then adding lactose into a fermentation system for second-stage fermentation to obtain natto; wherein the addition amount of the lactose is that 1-10% of the lactose is added on the basis that the mass of the dry beans is 100%. According to the method, special odor of traditional natto is removed, and the prepared natto powder has good nattokinase activity and a remarkable blood sugar reducing effect.

The invention belongs to the field of molecular biology, particularly relates to the field of tumor treatment, and particularly relates to application of a TRK inhibitor LYS-8 in preparation of a medicine for treating malignant tumors, particularly pancreatic cancer. LYS-8 is a small molecule TRK inhibitor with a novel structure, and research finds that LYS-8 can significantly inhibit TRK kinase activity and down-regulate downstream PI3K-AKT and other signal channels. Experimental results show that the inhibition effect of LYS-8 in pancreatic cancer cells is obviously superior to that of colorectal cancer cells, and the IC50 value of LYS-8 is lower; in an animal model, the tumor inhibition rate of LYS-8 on pancreatic cancer reaches about 70%, and the inhibition rate on colorectal cancer is about 56%, which is obviously superior to that of a colorectal cancer model. The invention reveals that LYS-8 has an unexpected curative effect advantage on pancreatic cancer, and a new drug choice is provided for targeted therapy of pancreatic cancer.

The present disclosure describes a recombinant yeast host cell having a first engineered metabolic pathway to convert fructose-6-phosphate (F-6-P) into acetyl-coenzyme A. The first engineered metabolic pathway comprises: a genetic modification for expressing a heterologous phosphoketolase capable of converting fructose-6-phosphate into erythrose-4-phosphate, and at least one genetic modification for decreasing native 6- phosphofructo-2-kinase activity classified under Enzyme Commission No. 2.7.1.105. Optionally, the recombinant yeast host cell comprises a second engineered metabolic pathway for convert acetyl-coA into a fermentation product. The present disclosure further describes a process for making a fermentation product. The process comprises contacting the recombinant yeast host cell described herein with a carbohydrate source under a condition allowing the conversion of at least a part of the carbohydrate into a fermentation product.

The invention relates to the technical field of blood detection, in particular to a formula of an optimized alanine aminotransferase kit, which has the technical scheme that lactic dehydrogenase, NADH (nicotinamide adenine dinucleotide), DCA-Na, glycerol and a Proclin-300 preservative are dissolved in a reagent I Tris buffer solution of the ALT kit; l-alanine, alpha-ketoglutaric acid, glycerol and a Proclin-300 preservative are dissolved in a Tris buffer solution of the reagent II, DCA-Na in the kit is an activator of a pyruvate-lactic dehydrogenase compound and inhibits the kinase activity of pyruvate dehydrogenase, glycerol is an enzyme activity stabilizer, Proclin-300 is a preservative, an instrument is used for detection at the main wavelength of 340 nm and the auxiliary wavelength of 380 nm, and the detection result is accurate. And calculating the ALT activity according to the decreasing rate of NADH (nicotinamide adenine dinucleotide).

Compounds of Formula (I) are provided, as well as compositions and methods of use thereof, wherein values of variables R1, R2, R5, X, X1 and X2 are provided herein. The compounds inhibit salt-inducible kinase activity and are useful in the treatment of various inflammatory diseases.

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.

This invention relates to the pharmaceutical field, specifically to a heteroindole derivative, its synthesis method, and its applications. The heteroindole compound derivative has the structure shown in general formula (I), wherein R1 is selected from any one of N-Boc-trans-1,4-cyclohexanediamine, N-Boc-piperazinyl, trans-1,4-cyclohexanediamine, piperazinyl, and N-methylpiperazinyl; R2 is selected from H or a halogen atom; and X, Y, and Z are all selected from CH or N. This invention demonstrates through experiments that the heteroindole derivative possesses good CDK9 inhibitory activity and selectivity, providing a theoretical basis for the treatment of diseases related to the activity or expression level of the cell cycle-dependent kinase CDK9, and exhibits good pharmaceutical potential.

Provided are nucleic acids encoding kinase-modulated bioluminescent indicator (KiMBI) polypeptides. In certain embodiments, a nuclei acid of the present disclosure encodes a KiMBI polypeptide comprising a first bioluminescent enzyme fragment, a phospho-binding domain, a 5 second bioluminescent enzyme fragment capable of forming an active bioluminescent enzyme with the first fragment via enzyme fragment complementation, and a kinase substrate bound by the phospho-binding domain when phosphorylated. KiMBI polypeptide may be fused to one or more fluorescent proteins, e.g., which exhibit resonance energy transfer (RET). Also provided are KiMBI polypeptides encoded by the nucleic acids of the present disclosure. Cells that express 10 a KiMBI polypeptide are also provided, as are non-human animals comprising such cells. Also provided are methods of assessing activity of a kinase of interest in a non-huma animal, and methods of assessing a test agent for the ability to inhibit a kinase of interest in a non-human animal.

T lymphocytes play a key role in the immune response and their functions are intimately linked to metabolic programs. During immune responses, T cells undergo a metabolic reprogramming notably characterized by an increased aerobic glycolysis. Using a quantitative phosphoproteomic approach, the inventors have identified a new transcription factor called Foxk1 as being highly phosphorylated in T cells upon T Cell Receptor (TCR) engagement. The results also indicate that Foxk1 phosphorylation and nuclear translocation is dependent of the AKT-mTOR kinase activities. Using T-cell specific Foxk1 deficient mice (Foxk1- / -), we demonstrated that Foxk1 is required for full T cell activation. Foxk1-deficient T cells exhibited reduced proliferation and cytokine secretion following TCR stimulation. Furthermore, T cells from Foxk1- / - mice were less prone to acquire an effector like phenotype than wild-type cells when challenged in vivo. Conversely, Foxk1 overexpression in T cells enhanced their effector functions in a TCR-dependent manner. In CD8+ T cells, this effect also results into enhanced cancer cell killing capacity in vitro, and improved tumor rejection in vivo. Altogether, these results indicated that Foxk1 is a major regulator of T cell metabolism and thus, of T cell effector functions. Thus, the present invention relates to host immune cells engineered to overexpress a Foxk1 polypeptide and their use of the treatment of cancer.

The present invention relates to the technical field of medicines. Specifically disclosed is a compound as represented by formula I′, or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof, symbols therein being as defined in the claims. The compound of the present invention may be used as a drug for regulating RET kinase activity or treating RET-related diseases, and has good pharmacokinetic properties.

The present invention provides a malonate salt form of (R)-3-(4-(7H-pyrrolo [2, 3-d] pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropionitrile and a crystal form thereof, the salt or crystal form can be used to modulate the activity of JAK kinase, and can be used to treat diseases associated with the activity or expression level of JAK kinase, such as JAK kinase. Including, for example, immune-related diseases, skin diseases, myeloproliferative disorders, cancer, and other diseases.

A compound of formula (I) having an inhibitory effect on HPK1 kinase activity, and a pharmaceutical composition comprising said compound. Use of said compound in the prevention and / or treatment of cancer, tumors, inflammatory diseases, autoimmune diseases, or immune-mediated diseases is also provided.

The application discloses application of an ethanol extract of Camellia oleifera flower buds as an EGFR inhibitor in preparation of a drug for treating non-small cell lung cancer. In the application, the ethanol extract of Camellia oleifera flower buds for treating non-small cell lung cancer is obtained by extracting Camellia oleifera flower buds with a solvent of 70% ethanol. The ethanol extract can inhibit EGFR kinase activity, can be used as an EGFR inhibitor, can inhibit proliferation of non-small cell lung cancer A549 cells by inducing G1 phase arrest, can induce apoptosis and inhibit migration and invasion through a mitochondria-mediated pathway, and can further play an antitumor role, and has a prospect of new drug research and development for treating non-small cell lung cancer.

The invention provides application of HIPK2 and an inhibitor thereof in preparation of drugs for preventing or treating aortic valve calcification, it is found that the enzyme activity of HIPK2 is closely related to aortic valve calcification, regulation and control of the kinase activity of HIPK2 through the HIPK2 inhibitor may be a potential target spot for treating aortic valve calcification, and the HIPK2 inhibitor is matched to regulate and control the kinase activity of HIPK2, so that the aortic valve calcification can be treated. The technical problem of non-surgical drug treatment of aortic valve calcification diseases is solved, an effective drug treatment means is provided for the aortic valve calcification diseases, and the application prospect is good.

The invention provides a soda water beverage added with nattokinase and a preparation method and application thereof, the soda water beverage added with nattokinase has a pH value of 7.8-8.2 and a carbonation degree of 0.8-1.2 g / L, and contains nattokinase, and the activity of the nattokinase is greater than or equal to 10,000 FU / L. The soda water beverage added with the nattokinase is applied to preparation of products for regulating PCSK9 activity, reducing the low density lipoprotein cholesterol LDL-C level in blood or preventing / assisting in managing obesity and related metabolic syndromes. The product is a beverage, a health food or a dietary supplement. The nattokinase can be used for specifically hydrolyzing the Ser153-Gly154 site of the PCSK9 protein, and the Ser153-Gly154 site of the PCSK9 protein can be specifically hydrolyzed. According to the beverage, the activity of nattokinase is protected by optimizing pH and a carbonation system, the intestinal absorption rate of the nattokinase is improved, and the function of PCSK9 is inhibited in a targeted manner so as to regulate blood lipid metabolism. Compared with an existing oral enzyme preparation, the oral enzyme preparation has high efficiency, stability and consumption convenience, and an innovative diet intervention scheme is provided for obesity and related metabolic diseases.

The application discloses an amide compound containing a pyrimidine structure and application thereof in preparation of a TYK2 JH2 kinase inhibitor, and relates to the technical field of compound preparation.The application provides an amide compound containing a pyrimidine structure, which can effectively block IL-12 / IL-23 and type I interferon signaling pathways by inhibiting TYK2 JH2 kinase activity with high selectivity, and significantly improve the pathological process of autoimmune diseases (such as psoriasis, colitis, systemic lupus erythematosus and the like); the compound has the advantages of low toxic side effect and high targeting, can precisely regulate abnormal immune response, and can provide various dosage forms (tablets, capsules, injection agents and the like), support oral or injection administration, and has both curative effect and medication convenience, and therefore provides a safe and efficient novel drug scheme for autoimmune disease treatment.

Solid forms of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphic forms, cocrystals, and amorphous forms thereof, and pharmaceutical compositions thereof.

This invention discloses a method for preparing functional plant ethylene receptor ETR1 dimers, along with its activity detection method and applications. The preparation method includes expressing tagged ethylene receptor ETR1 protein in a Pichia pastoris expression system, extracting ETR1 protein from membrane fractions, performing two-step affinity chromatography purification, and enriching with size exclusion chromatography to obtain biologically active ETR1 dimers. The activity detection method involves pre-incubating different concentrations of ETR1 dimers with copper ions and / or ethylene, reacting with ATP, and finally assessing its ligand-dependent kinase activity by measuring the luminescent signal associated with the remaining ATP. The advantage of this invention is that it achieves the first controllable preparation of functional ethylene receptor ETR1 dimers in a eukaryotic system and establishes a sensitive, strictly dimer-state-dependent, and copper / ethylene synergistic in vitro detection system. This system can be used for precise assessment of ETR1 protein functional sites and for high-throughput screening of potential ethylene receptor agonists or antagonists.

The present disclosure features compounds and related compositions that, inter alia, modulate cyclin K (CCNK) and / or cyclin dependent kinase (CDK) activity, e.g., CDK12 or CDK13 activity, and methods of use thereof.

The present application relates to substituted pyrrole carboxamide derivatives of Formula (I) that modulate the activity of the cell division cycle 7-related kinase (Cdc7). Accordingly, the compounds of the present application are useful in the treatment of diseases associated with dysregulated kinase activity, such as cancer, cell proliferative disorders, viral infections, immune disorders, neurodegenerative disorders, cardiovascular diseases, and bone-related diseases. The present application also provides methods for making these compounds, pharmaceutical compositions comprising these compounds, and their medical uses.