4 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.

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.

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.