19 results about "Kinase signaling" patented technology

2-diarylmethyl-4-aminotetrahydropyran derivatives are disclosed. The compounds include the following genus:or a pharmaceutically acceptable salt thereof. The compounds activate cellular PP2A, suppress oncogenic kinase signaling and negatively regulate MYC and MYCN in cancer. The compounds also induce FOXO transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a monotherapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.

A multi-target kinase inhibitor is shown in formula (I), in which R is selected from formula (a), formula (b), formula (c), formula (d), formula (e) and formula (f). The multi-target kinase inhibitor can effectively inhibit the enzymatic activities of RET, VEGFR3 and PDGFRA, and can effectively treat diseases that are regulated and controlled by multi-target kinases and are related to abnormal signal transduction pathways of the multi-target kinases, including cancers of breast, respiratory tract, brain, reproductive organ, digestive tract, urinary tract, eye, liver, skin, head and / or neck and distant metastatic cancers thereof, and lymphoma, sarcoma, leukemia and the like. The active ingredients of the pharmaceutical composition of the present invention comprise a multi-target kinase inhibitor, which accounts for 1-50 wt % of the composition.

2-diarylmethyl-4-aminotetrahydropyran derivatives are disclosed. The compounds include the following genus:or a pharmaceutically acceptable salt thereof.The compounds activate cellular PP2A, suppress oncogenic kinase signaling and negatively regulate MYC and MYCN in cancer. The compounds also induce FOXO transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a monotherapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.

Provided is the use of a CSF1R kinase inhibitor compound or a pharmaceutically acceptable salt thereof in the preparation of drugs for treating diseases related to the CSF1R kinase signal transduction pathway or drugs for regulating immunization.

2-diarylmethyl-4-aminotetrahydropyran derivatives are disclosed. The compounds include the following genus:or a pharmaceutically acceptable salt thereof.The compounds activate cellular PP2A, suppress oncogenic kinase signaling and negatively regulate MYC and MYCN in cancer. The compounds also induce FOXO transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a monotherapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.

The invention relates to therapeutic and prognostic use based on the findings obtained as a result of investigating the effectiveness of different miRNAs on the expression levels of some genes involved in the Janus Kinase-Signal Transducer Transcription Activator (JAK-STAT) pathway in the treatment of respiratory form distemper.

3-Diarylmethylenes are disclosed. The compounds activate PP2A, suppress oncogenic kinase signaling, and negatively regulate MYC and MYCN in cancer. The compounds also induce FOXO transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a monotherapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.

3-Diarylmethylenes are disclosed. The compounds activate PP2A, suppress oncogenic kinase signaling, and negatively regulate MYC and MYCN in cancer. The compounds also induce FOXO transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a monotherapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.

The invention provides a CSF1R kinase inhibitor compound or a pharmaceutically acceptable salt thereof and application of the CSF1R kinase inhibitor compound or the pharmaceutically acceptable salt thereof in medicines for treating diseases related to a CSF1R kinase signal transduction pathway or regulating immunity.

Combined treatment with a SIRPα-4-lBBL fusion protein for cancer is provided. Accordingly, there is provided a combination of a SIRPa-4-lBBL fusion protein and at least two agents selected from the group consisting of an agent which inhibits activity or expression of a receptor-ligand combination PD1-PD-L1, an agent which inhibits activity or expression of a receptor-ligand combination VEGFR-VEGF, and Trifluridine / Tipiracil, for use in treating cancer in a subject in need thereof. Also provided a combination of a SIRPa-4-lBBL fusion protein and agent which inhibits a receptor tyrosine kinase signaling pathway, for use in treating cancer in a subject in need thereof.

A method for inhibiting the release of tumor necrosis factor (TNF) from mast cells including administering an effective amount of an inhibitor to a subject; wherein the inhibitor is an inhibitor that selectively targets conventional mitogen activated protein kinase signaling pathways; and allowing the inhibitor to interact with mast cells or their signaling pathways involved in TNF release, thereby inhibiting TNF release. Also disclosed is a method for preventing the conversion of membrane-bound tumor necrosis factor (mTNF) to soluble tumor necrosis factor (sTNF) in mast cells using an inhibitor including administering an effective amount of the inhibitor to a subject; wherein the inhibitor is a chemical compound that selectively targets conventional mitogen activated protein kinase signaling pathways; and allowing the inhibitor to interact with mast cells or the enzymatic machinery responsible for the cleavage of mTNF within mast cells, thereby inhibiting the conversion of mTNF to sTNF.

The invention discloses application of stem cell factor polypeptide and derivatives thereof in preparation of medicines for preventing and treating Alzheimer's disease and other neurodegenerative diseases, and belongs to the technical field of biological medicines. A plurality of experiments including a neuronal cell and Alzheimer disease double-transgenic animal model prove that the stem cell factor can effectively inhibit neuronal endoplasmic reticulum stress and related cell apoptosis through a Janus kinase / signal transduction and transcriptional activator pathway; therefore, Alzheimer's disease and other neurodegenerative diseases can be effectively prevented and / or treated. The invention provides a new pharmacological approach and a prevention and treatment strategy for research and development of new drugs for sporadic and familial Alzheimer's disease and other neurodegenerative diseases, and has a good application prospect in the field of biological medicines.

The present disclosure relates to implantation or proliferation of cells in fat-related lymphatic clusters ("FALC" or "milk spots"), which can be used to generate functional ectopic tissues. The present disclosure also provides methods and compositions for transplanting and proliferating cells in FALC by activating lymphotoxin beta receptor (LTbeta R) and / or NF-[kappa] B-induced kinase (NIK) signal transduction pathways. The disclosure also provides methods and compositions for establishing ectopic liver tissue in FALC (breast spot) and using such ectopic liver tissue for obtaining therapeutic benefits, and methods and compositions for generating ectopic kidney tissue in FALC, which can be used for obtaining therapeutic benefits in a subject.

The invention discloses an anti-photoaging active composition which is composed of 75-97 parts of tea extract, 1-19 parts of hexapeptide-9 and 1-8 parts of carnosine, oxidative stress reaction is inhibited by reducing the ROS content in the body according to different proportions of the three active substances, cascade reaction of mitogen activated protein kinase signal channels is further inhibited, and the anti-photoaging active composition has a good anti-photoaging effect. Aging damage caused by ultraviolet radiation is effectively reduced, and a good anti-wrinkle effect is achieved. Meanwhile, the optimal compatibility proportion of the three active matters for exerting the anti-photoaging effect is determined, the anti-photoaging active composition can be used in the field of cosmetics, the formula cost can be reduced, the anti-photoaging effect can be effectively improved, and the anti-photoaging active composition has high market popularization value. The invention also discloses application of the anti-photoaging active composition in preparation of cosmetics for preventing skin photoaging.

To provide compounds, compositions thereof, and methods of using the same.SOLUTION: Compounds provided by this invention are also useful for the study of IRAK enzymes in biological and pathological phenomena; the study of intracellular signal transduction pathways occurring in bodily tissues; and the comparative evaluation of new IRAK inhibitors or IRAK degraders or other regulators of kinases, signaling pathways, and cytokine levels in vitro or in vivo.SELECTED DRAWING: None

Use of a compound of general formula (A) which is a CFS-IR kinase inhibitor or a pharmaceutically acceptable salt thereof in the preparation of medicaments for treating diseases related to CSF-1R kinase signal transduction pathway or medicaments for regulating immunization. In vivo and in vitro studies show that the compound can significantly inhibit CSF-IR kinase activity; significantly inhibits the proliferation of a CSF-1 / CSF-1R-driven mouse myeloid leukemia cell line, inhibits the survival of macrophages induced by CSF-1 and reverses M2 polarization phenotype of macrophages, and has an effect superior to that of the marketed medicament Pexidartinib. In a TAM enriched tumor model (MC38 model), the compound significantly antagonizes the tumor immunosuppressive microenvironment and exhibits significant anti-tumor efficacy. The compound has inhibitory effects on tumors that are not sensitive to immune checkpoint drugs, and can enhance the efficacy of immune checkpoint drugs, and has good clinical application prospects.

The application discloses a covalent kinase inhibitor, a preparation method, a pharmaceutical composition and application, the structure of the covalent kinase inhibitor is as shown in formula I, II, III, IV or V, and the covalent kinase inhibitor further comprises a pharmaceutically acceptable salt thereof, the covalent kinase inhibitor can be efficiently covalently combined with a target kinase, and simultaneously triggers the release of NO / NO2 — ; on one hand, the covalent combination can covalently inhibit the target kinase containing a sulfydryl group, and on the other hand, the released NO / NO2 — can further produce sulfydryl nitroso modification on the target kinase or a protein interacting with the target kinase, thereby inhibiting self-phosphorylation, preventing kinase signal transduction and playing a synergistic effect; the covalent kinase inhibitor can act on various kinases related to malignant tumor proliferation, has good selectivity and a low off-target effect, can significantly inhibit the growth of tumor cells at a cell and animal level, and has no obvious adverse reactions. In addition, the preparation method is simple and universal, and is conducive to the expansion of a mother nucleus structure of various other kinase inhibitors.

Disclosed in the present invention are a covalent kinase inhibitor, a preparation method, a pharmaceutical composition and the use. The covalent kinase inhibitor has a structure as shown in formula (I), (II), (III), (IV) or (V), and further comprises a pharmaceutically acceptable salt of the covalent kinase inhibitor, which can efficiently and covalently bind to a target kinase, and simultaneously trigger the release of NO / NO2 —. Covalent binding can realize covalent inhibition of a sulfydryl-containing target kinase, and the released NO / NO2 — can further perform S-nitrosylation modification on a target kinase or a protein interacting with the target kinase, so as to inhibit the phosphorylation of the target kinase or the protein, prevent kinase signaling, and provide a synergistic effect. The covalent kinase inhibitor can act on a variety of kinases associated with malignant tumor proliferation, has good selectivity and a low off-target effect, significantly inhibits the growth of tumor cells at both cell and animal levels, and has no obvious adverse reaction. In addition, the preparation method is simple and universal, which is beneficial to the expansion of the parent nucleus structures of other multiple kinase inhibitors.

3-Diarylmethylenes are disclosed. The compounds activate PP2A, suppress oncogenic kinase signaling, and negatively regulate MYC and MYCN in cancer. The compounds also induce FOXO transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a monotherapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.