7 results about "Pim kinases" patented technology

Disclosed in the present invention are a PIM kinase inhibitor as shown in general formula II, a pharmaceutical composition thereof, a preparation method therefor and the use thereof in the preparation of a drug for preventing and / or treating indications related to a PIM signaling pathway. The compound of the present invention is an ideal PIM kinase inhibitor with a high activity, which can be used for treating and / or preventing diseases including autoimmune diseases and tumors, e.g., inflammatory bowel disease, hematologic malignancies such as acute myeloid leukemia, myelofibrosis and chronic lymphocytic leukemia, and solid tumors such as gastric cancer and prostate cancer.

The present invention relates to a combination of a PIM kinase inhibitor and a KRAS inhibitor for use in treating cancer in a subject in need of such treatment. Compositions or kits containing the same are also provided. The present invention also relates to a PIM kinase inhibitor for use in treating cancer with a KRAS mutation in a human subject in need of such treatment.

Inventors have firstly demonstrated that the transcriptomic signature of PTENpc- / - LSCmed cells is enriched in human MSPC signature, associated to metastases and ADT resistance. Using scRNAseq specifically with sorted PTENpc- / - LSCmed cells, they identified three distinct LSCmed clusters and showed that castration favors the emergence of the most stem-like LSCmed subpopulation by cell plasticity. In the latter, they identified the transcription factor FOSL1 / AP-1 and the kinase PIM1 as relevant therapeutic targets, and they showed that combined inhibition using JQ1, a BET / AP-1 inhibitor, and CX-6258, a pan-PIM kinase inhibitor, efficiently prevents PTENpc / - LSCmed cell growth in organoids. These findings were confirmed in the human prostate HPV10 cell line here identified as a robust model of Club / Hillock cells. Combined drug delivery to castrated PTEN-null mice induced a significant prostate weight decrease associated with the reduction of histopathological phenotypes and dramatically altered organoid-formation capacity of LSCmed cells sorted from these tumors. Accordingly, the drug combination significantly delayed tumor growth of MSPC-like human PC-3 cells subcutaneously injected into castrated immunodeficient mice. Altogether, this work shows a new therapeutic potential of combined FOSL1 and PIM1 targeting to prevent, or at least delay, the growth of MSPC-like cells. Accordingly, the invention relates to i) an inhibitor of FOSL1 and ii) an inhibitor of PIM1, as a combined preparation for use in the treatment of prostate cancer in a subject in need thereof.

The present invention provides protein kinase having one of the following structures (I), (II) or (III):or a stereoisomer, prodrug, tautomer or pharmaceutically acceptable salt thereof, wherein R, R1, R2 and X are as defined herein. Compositions and methods for using the same in the treatment of cancer, autoimmune, inflammatory and other Pim kinase-associated conditions are also disclosed.

Provided is a composition comprising a polyglycolized glyceride and a compound having the following structure (I):or a pharmaceutically acceptable salt thereof. Also provided are crystalline forms of the compound of structure (I), or a pharmaceutically acceptable salt thereof. Methods of making the same, and methods for using the same in the treatment of cancer, autoimmune, inflammatory and other Pim kinase-associated diseases, disorders or conditions are also disclosed.

It relates to the combination of PIM kinase inhibitor and a KRAS inhibitor for use in treating cancer, in a subject in need thereof. Also provided are compositions or kits comprising same. Furthermore, it also relates to a PIM kinase inhibitor for use in treating cancer with KRAS mutation in a human subject in need thereof.

The application provides a compound with a structure shown in a general formula (I), a deuterium compound, a stereoisomer or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the same and a use thereof. The compound provided by the application has a good PIM kinase inhibition effect, is a novel, high-activity and low-toxicity ideal PIM inhibitor, and can be used for treating and / or preventing diseases such as acute myeloid leukemia, myelofibrosis, chronic lymphocytic leukemia, blood tumors such as gastric cancer and prostate cancer, and solid tumors.