157 results about "MEK inhibitor" patented technology

Disclosed is a pharmaceutical composition for the treatment of tumors, the pharmaceutical composition comprising (6S, 9aS)-N-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl) azetidin-1-yl] pyridin-2-yl} methyl)-6-(2-fluoro-4-hydroxybenzyl)-4, 7-dioxo-2-(propyl-2-en-1-yl) hexahydro-2H-pyrazino [2, 1-c] [1, 2, 3] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [ The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof and administered in combination with a MEK inhibitor.

The present invention relates, in part, to methods, compounds, and compositions of KRAS G12D inhibitors in combination with dual RAF / MEK inhibitors for the treatment of abnormal cell growth (e.g., cancer).

The present disclosure provides compounds, compositions containing such compounds, and methods of designing, developing, producing and preparing compounds represented by general Formula (I), including pharmaceutically acceptable salts thereof or a synthetic intermediate thereof:The compounds act as MEK inhibitors and are capable of displaying one or more beneficial therapeutic effects, including treating cancer.

The invention relates to polymorphic substances of a benzothiazole compound as a protein kinase Mek inhibitor, and a preparation method and medical application of the polymorphic substances.

The discovery of mutant or fusion kinases that drive oncogenesis, and the subsequent approval of specific inhibitors for these enzymes, has been instrumental in the management of some cancers. However, acquired resistance remains a significant problem in the clinic, limiting the long-term effectiveness of most of these drugs. Herein is demonstrated a strategy to overcome this resistance through drug-induced MEK cleavage (via direct procaspase-3 activation) combined with targeted kinase inhibition. This combination effect is shown to be general across diverse tumor histologies (melanoma, lung cancer, and leukemia) and driver mutations (mutant BRAF or EGFR, fusion kinases EML4-ALK and BCR-ABL). Caspase-3-mediated degradation of MEK kinases results in sustained pathway inhibition and substantially delayed or eliminated resistance in cancer cells in a manner superior to combinations with MEK inhibitors. These data suggest the generality of drug-mediated MEK kinase cleavage as a therapeutic strategy to prevent resistance to targeted anticancer therapies.

The present invention relates to a pharmaceutical combination comprising a cyclin dependent kinase (CDK) inhibitor represented by a compound of formula I (as described herein) or a pharmaceutically acceptable salt thereof; and at least one anticancer agent selected from a BRAF inhibitor or a MEK inhibitor, for use in the treatment of melanoma. The present invention also relates to a method for the treatment of melanoma comprising administering to a subject in need thereof, a therapeutically effective amount of a CDK inhibitor and a therapeutically effective amount of at least one anticancer agent selected from a BRAF inhibitor or a MEK inhibitor.

The present invention is directed to a combination therapy involving Pioglitazone and a MEK inhibitor for the treatment of a cancer patient in need of such a therapy.

The present invention relates to MEK inhibitors that can show one or more beneficial therapeutic effects. The MEK inhibitors can be used to prevent and / or treat Hantavirus infection.

This disclosure relates to pharmaceutical combinations for treating and / or preventing cancer and methods and uses thereof. More particularly, provided are pharmaceutical combination comprising a PRMT5 Inhibitor and a cellular activity modulator selected from an EGFR inhibitor, a KRAS inhibitor, a KRAS-G12C inhibitor, a MEK inhibitor, a Bcl-2 inhibitor, a SOS1 inhibitor, a PARP inhibitor, a RAF inhibitor, a ERK inhibitor, a CDK4 / 6 inhibitor, a MALT1 inhibitor, a BTK inhibitor, MAT2A inhibitor, a PI3K inhibitor, a AKT inhibitor, a FGFR inhibitor, a Type I PRMT inhibitor, a STING agonist, or an immune checkpoint inhibitor / modulator.

The present invention relates to combination therapies for treating cancers associated with genetic alterations in the MAPK pathway and / or EGFR. In particular, the present invention relates to a method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of an SOS1 inhibitor and a MEK inhibitor, pharmaceutical compositions comprising such compositions, kits comprising such compositions, and methods of use thereof.

To provide a culture medium for inducing directional differentiation of mouse intestinal organoids into intestinal endocrine cells and applications therefor.SOLUTION: A Mek inhibitor PD0325901, a Wnt inhibitor IWP-2 and a Notch inhibitor DAPT are added into a mouse small intestine organoid standard condition (ENR) culture medium, to induce mouse small intestine organoids to be differentiated into mature intestinal endocrine cells, thereby achieving the construction of the mouse intestinal endocrine cell induction model. The induction culture medium is used to induce mouse intestinal organoids to be differentiated into intestinal endocrine cells. The culture medium is replaced every two days following the initiation of differentiation of mouse small intestine organoids. Following 4 days of differentiation, the culture solution is removed by aspiration. A PBS buffer is added and sprayed, followed by centrifugation and removal of a supernatant. Resuspension is conducted in 4°C Advanced DMEM, followed by centrifugation and removal of the supernatant, and then resuspension in Advanced DMEM and Matrigel.SELECTED DRAWING: Figure 4

A novel combination comprising the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)6S-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-al]pyrimidin-1-yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, with a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2 / 6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, pharmaceutical compositions containing the same and methods of using such combinations and compositions in the treatment of conditions in which inhibition of MEK and / or B-Raf is beneficial, e.g. cancer

Described herein is the combination of STING / TLR4 agonist nanoparticles (NPs) and a combination of a MEK inhibitor (e.g., trametinib) and CDK4 / 6 inhibitor (e.g., palbociclib) treatment. This combination synergizes to (a) lead to enhanced NP uptake in multiple cell types in the TME, (b) increased antigen presentation on tumors cells as well as APCs, and (c) CD8+ T cell mediated long-term tumor control that is interferon signaling dependent. Also provided are methods to treat cancer, e.g., KRAS mutant cancers, e.g., KRAS mutant PDAC or lung cancer.

The present invention relates to a polymorph of a benzothiazole compound as a protein kinase Mek inhibitor, and a preparation method therefor and the medical use thereof.

This disclosure relates to materials and method of using MEK inhibitors, such as the MAP2K inhibitor CI-1040 to treat a subject having an existing epileptic disorder or prevent epilepsy in a subject without an existing epileptic disorder following a brain injury alone or in combination with a second anti-epileptic drug such as an mTOR inhibitor.

Disclosed are novel compounds for use in treating a proliferative disorder such as a cancer. Further disclosed are compositions comprising the novel compounds. Methods of using the disclosed compounds and compositions are further described. The methods include administering one or more of the disclosed compounds for treatment of various proliferative disorders, including an HRAS-driven cancer, a KRAS-driven cancer, a NRAS-driven cancer, Ewing sarcoma, B-cell acute lymphoblastic leukemia, leukemia, lung cancer, non-small cell lung cancer (NSCLC), solid tumor, breast cancer, triple-negative breast cancer (TNBC), hormone-resistant triple negative breast cancer. Further described are combination therapies in which a novel compound is administered in combination with one or more of a MEK inhibitor, a KRAS G12C inhibitor, or a Selective Estrogen Receptor Degrader (SERD) to an individual in need thereof.

Provided in the present invention are a granular pharmaceutical composition comprising protein kinase Mek inhibitor benzothiazole, and the therapeutic use thereof.

The present disclosure relates to: a) crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide; b) pharmaceutical compositions comprising one or more crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide, and, optionally, one or more pharmaceutically acceptable carriers; c) methods of treating a tumor a cancer, or a Rasopathy disorder by administering one or more crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide to a subject in need thereof, and methods of producing essentially pure Form IV of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide.

The present invention relates, in part, to methods, compounds, and compositions of an autophagy pathway inhibitor in combination with a dual RAF / MEK inhibitor, for treating abnormal cell growth (e.g., cancer).

The invention discloses a drug combination of an MEK inhibitor and a PLC beta / PKC signal channel inhibitor and application of the drug combination in treatment of BRAF (V600E) mutation tumors, and belongs to the field of biological medicine. According to the invention, the PLC beta / PKC signal channel inhibitor and the MEK inhibitor are combined for use, so that the drug resistance can be reversed, stronger anti-BRAF (V600E) mutant tumor activity is shown, the growth of tumors is more effectively inhibited, and the defect of poor treatment effect or large toxic and side effects caused by single medication is overcome. Good application prospects are realized.

The present invention provides a method for preparing retinal pigment epithelial cells, comprising the following steps: (1) a first step of culturing pluripotent stem cells in a culture medium containing at least one selected from the group consisting of an FGF receptor inhibitor and a MEK inhibitor for a period of no more than 30 days, and (2) a second step of culturing the cells obtained in the first step in a culture medium containing at least one selected from the group consisting of a Rho signal transduction pathway inhibitor and a cell apoptosis inhibitor to form retinal pigment epithelial cells. Using this method, it is possible to prepare retinal pigment epithelial cells from pluripotent stem cells in a more efficient and convenient manner.

The present invention relates to a composition for enhancing the anti-cancer effect of a MEK inhibitor, the composition comprising aripiprazole as an active ingredient, and more specifically, to a composition for enhancing the anti-cancer effect of a MEK inhibitor, the composition comprising aripiprazole as an active ingredient, the composition is capable of treating cancer by acting as an anti-cancer effect enhancer of a MEK inhibitor when used in combination therapy with aripiprazole. When administered in combination with a MEK inhibitor, an effective amount of aripiprazole according to the present invention highly effectively improves the anti-cancer effect of the MEK inhibitor (e.g., by inducing cancer cell death), and thus the present invention can be effectively used as an agent for improving the anti-cancer effect of the MEK inhibitor.

The invention provides application of lactobacillus rhamnosus H23A017 combined with trametinib in preparation of drugs for treating melanoma, lactobacillus rhamnosus H23A017 is combined with MEK inhibitor trametinib in an intratumoral injection mode, it is found that compared with a single medication group, combined treatment can improve the expression level of IFN-gamma and TNF-alpha in a tumor microenvironment, and the effect of treating melanoma is achieved. The application has the advantages that tumor cell apoptosis is promoted, tumor cell infiltration is increased, the tumor volume is further reduced, and a new strategy is provided for development of low-toxicity and high-efficiency melanoma immune drug combination.

The present disclosure provides compounds, compositions containing such compounds, and methods of designing, developing, producing and preparing compounds represented by general Formula (I), including pharmaceutically acceptable salts thereof or a synthetic intermediate thereof:The compounds act as MEK inhibitors and are capable of displaying one or more beneficial therapeutic effects, including treating cancer.

The present disclosure provides compounds, compositions containing such compounds, and methods of designing, developing, producing and preparing compounds represented by general Formula (III), including pharmaceutically acceptable salts thereof or a synthetic intermediate thereof:The compounds act as MEK inhibitors and are capable of displaying one or more beneficial therapeutic effects, including treating cancer.

The present invention relates to polymorphs of a protein kinase Mek inhibitor benzothiazole compound, processes for their preparation, and their medical use.

The application discloses application of FTY720 as a PP2A phosphatase activator in preparation of a medicine for treating type I neurofibromatosis. The application first uses FTY720 for treatment of type I neurofibromatosis, and proves that FTY720 significantly inhibits formation of neurofibromas by non-specifically activating PP2A phosphatase. In-vivo experimental results show that FTY720 as a single drug can significantly inhibit tumor growth, and a synergistic effect is presented when FTY720 is combined with a MEK inhibitor, and tumor growth is almost completely inhibited. In-vitro cell experiments show that FTY720 as a single drug or in combination with MEKi treatment can inhibit tumor Schwann cells from forming tumor spheres, inhibit cell proliferation and migration, and induce tumor cell apoptosis. The application overcomes the drug resistance problem existing in the prior art MEK inhibitor, and provides a new treatment strategy for type I neurofibromatosis. FTY720 is an FDA-approved drug, and has good safety and drugability, and has high clinical conversion potential.

The present invention relates to combination therapies for treating cancers associated with genetic alterations of the MAPK pathway and / or EGFR. In particular, the present invention relates to methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of a SOS1 inhibitor and MEK inhibitor, pharmaceutical compositions comprising a such compositions, kits comprising such compositions and methods of use therefor.