302 results about "Kinase activity" 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 formulae (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.

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 invention provides compounds of formulae (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.

The invention provides a halogenated indolone compound and a preparation method and application thereof, a halogenated indolone derivative and application thereof, and a pharmaceutical composition and application thereof, and relates to the technical field of biological medicines. Kinase spectrogram analysis shows that the halogenated indolone compound provided by the invention not only has VEGFR (vascular endothelial growth factor receptor), FGFR (fibroblast growth factor receptor) and PDGFR (plasma derived growth factor receptor) kinase inhibitory activity, but also has very strong AXL kinase inhibitory activity, and the IC50 value reaches a low nanomole level and is 45 times of the AXL kinase inhibitory activity of nintedanib. The halogenated indolone compound provided by the invention shows better anti-tumor activity than nintedanib at a cellular level and in an animal body, has better effects of inhibiting tumor invasion and metastasis than nintedanib, and can effectively treat malignant tumors and invasion and metastasis thereof.

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 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.

Provided herein are methods of treating, preventing, or delaying the onset of heart diseases such as cardiomyopathy and heart failure by administering a treatment compound to a subject in need thereof. The present disclosure further relates generally to methods of improving cardiac efficiency using the treatment compound to a subject in need thereof. The present disclosure also relates generally to methods of inhibiting the activity of a pyruvate dehydrogenase kinase (PDK) using the treatment compound to a subject in need thereof. The treatment compound is a compound of formula (I), or a pharmaceutically acceptable salt, solvate, or a prodrug thereof.

The invention relates to the technical field of medicines, in particular to a compound with an unsaturated alkane functional group and a preparation method and application thereof, and the compound has JAK kinase inhibitory activity. The invention provides a compound as shown in a formula I or a stereoisomer, a tautomer and pharmaceutically acceptable salt thereof, and the compound with an unsaturated alkane functional group has excellent JAK3 kinase inhibition effect, high biological activity, better drug effect and higher selectivity, and can be used as a JAK3 kinase inhibitor for treating various diseases with abnormal JAK3 kinase activity. # imgabs0 #

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 relates to new pyrrolopyridine compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibition of JAK1 and JAK3 kinase activity in a human or animal subject are also provided for the treatment diseases such as pruritus, alopecia, androgenetic alopecia, alopecia areata, vitiligo and psoriasis.

The invention relates to the technical field of biology, and discloses application of a cucumber CsTOR gene in cucumber grafted seedlings, and the cucumber CsTOR gene has high expression level in tender tissues of root tips, stem tips and male flower buds of cucumbers; subcells of the cucumber CsTOR gene are localized in a cell nucleus and a cell membrane; the cucumber CsTOR gene is used for regulating and controlling the survival rate of cucumber grafted seedlings. The cucumber-pumpkin grafted seedlings treated by a control group and the TOR inhibitor are further subjected to transcriptome and metabolome analysis, and it is found that after the TOR kinase activity is inhibited, the content of plant hormone metabolism related genes and hormones is remarkably changed, especially auxin. The CsTOR-mediated auxin-regulated grafting interface healing mechanism research is preliminarily disclosed, and while the research on the heterologous grafting interface healing mechanism is enriched, theoretical support is provided for creating a rapid healing material and optimizing a grafted cucumber production technology in the future.

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 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.

Disclosed are compositions and methods for treating a disease or disorder such as cancer in a subject in need thereof. In some embodiments, the methods include administering to the subject a vector that has a first nucleic acid sequence encoding a promoter operably linked to each of a second nucleic acid sequence encoding a therapeutic polypeptide, and a third nucleic acid sequence encoding a peptide domain that is stabilized when phosphorylated by kinase activity in a target cell and / or tissue. In some embodiments, the target cell and / or tissue can be a cell and / or tissue undergoing a stress response. In some embodiments, the target cell and / or tissue can be a cell and / or tissue in which a CK2 kinase is active. The kinase activity can be elevated extracellular regulated kinase (ERK) activity, p38 MAP kinase activity, and / or CK2 activity.

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 present invention describes solid forms and complexes of chemical compounds that modulate kinase activity, including PI3 kinase activity, pharmaceutical compositions, and methods of treating diseases and disorders associated with kinase activity, including PI3 kinase activity. The present invention also provides methods for preparing compounds, polymorphic forms, co-crystals and their amorphous forms, and pharmaceutical compositions thereof.