172 results about "Kinase activity" patented technology

Disclosed are a kinase inhibitor and a pharmaceutical composition comprising the kinase inhibitor. The kinase inhibitor comprises a compound as represented by formula (I) or a pharmaceutically acceptable salt, solvate, ester, acid, metabolite, or prodrug thereof. The compound and composition above can inhibit wild-type KIT and / or mutant KIT tyrosine kinase activity and treat, prevent, or alleviate diseases, disorders, or conditions associated with wild-type KIT and / or mutant KIT kinase activity.

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 invention concerns a compound of formula (I):or one of its pharmaceutically acceptable salts, especially for use as inhibitors of the ERK kinase activity, in particular ERK2 activity.

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.

Aminopyrimidine containing compounds that inhibit both Mer tyrosine kinase (MerTK) activity and Tyro3 kinase activity are disclosed herein. Additionally disclosed are methods of synthesis and use of the aminopyrimidine containing compounds as anti-cancer agents, immunostimulatory and immunomodulatory agents, anti-platelet agents, anti-infective agents, and as adjunctive agents.

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 present invention discloses the application of Alternariol in the preparation of diabetes prevention and treatment drugs, which belongs to the field of medical technology. The present invention first screens out the compound Alternariol through in vitro DYRK1A kinase activity experiment, and its IC 50 The value was 20μM. Then, through INS-1 cell proliferation model experiments, it was found that the compound Alternariol can promote INS-1 cell proliferation and promote insulin secretion by pancreatic islet cells. Even at very low concentrations, such as 300nmol, it can significantly promote INS-1 cell proliferation. Finally, through mouse diabetes model experiments, it was further verified that the compound Alternariol can indeed control blood sugar in T1D mice and promote pancreatic proliferation in mice, while also having no toxic effects on the mouse body. This invention has extraordinary significance for T1B diabetes with impaired pancreatic cell function.

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.

This invention discloses a compound of formula (I), or its stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, hydrates, or solvates, wherein X is a sulfur atom or an oxygen atom; and R is optionally an aliphatic substituted amino group, aniline group, or phenolic group. This invention also discloses pharmaceutical compositions containing the compound of formula (I). The compound of formula (I) exhibits excellent DCLK1 kinase activity inhibition ability and can be used to prepare DCLK1 kinase inhibitors, drugs for the prevention and / or treatment of inflammation or cancer.

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.

To provide compounds and compositions capable of modulating PINK1 kinase activity, and methods for producing and using the same.SOLUTION: A compound has a structure in the figure. (In the formula: Z is O, NH, or CH2; R1a, R1b, R1c and R1d are H, halogen, CN, NH2, or the like; and R2 is -(CH2)nCy1, -O(CH2)nCy1, Cy1, or the like, where Cy1 is C4-C9 cycloalkyl, C3-C9 heterocycle, or the like.)SELECTED DRAWING: Figure 1A

The disclosure is directed to nitrogen-containing heteroaryl analogs, methods of making nitrogen-containing analogs, and methods of treating disorders associated with PINK1 kinase activity including, but not limited to, neurodegenerative diseases, mitochondrial diseases, fibrosis, and / or cardiomyopathy using these analogs. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

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.

The present invention is directed to the compounds of Formula (A)—inhibitors of EGFR. The inhibitors described herein can be useful in the treatment of diseases or disorders associated with EGFR, such as is lung cancer. In particular, the invention is concerned with compounds and pharmaceutical compositions inhibiting EGFR kinase activity in a cell, methods of treating diseases or disorders associated with EGFR, and methods of synthesizing these compounds.

In one aspect, the disclosure relates to composition and methods for proteolysis-targeting chimeric molecules (PROTACs). In some aspects, the disclosed compounds are useful for modulating LCK tyrosine kinase activity through targeted degradation. In some aspects, the disclosed compounds are orally bioavailable. In further aspects, the present disclosure relates to methods of making the disclosed compounds, pharmaceutical compositions comprising the disclosed compounds, and methods of treating various clinical conditions and disorders using the same, such as T-cell acute lymphoblastic leukemia. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.