83 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 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 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.

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.

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

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 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 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 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 a pharmaceutically acceptable salt of compound N-(2-hydroxy-ethoxy) 4-fluoro-5-(2-fluoro-4-iodophenylamino)-1H-benzo[d]thiazole-6-carboxamide and the use of said pharmaceutically acceptable salt in the treatment of cancers.

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

Compositions and methods for making pluripotent cells. In particular, a culture platform for making pluripotent cells with ground state pluripotency. In various embodiments, compositions comprising: (a) a Wnt pathway agonist; (b) a MEK inhibitor; and (c) a ROCK inhibitor. In certain embodiments, the composition further comprises a bFGF or a LIF.

The present invention concerns the use of an L-type calcium channel (LTCC) blocker in combination with a BRAF inhibitor (BRAFi) and / or a MEK inhibitor (MEKi) for the treatment of melanoma in a patient.

A method of identifying a subject having cancer who is likely to benefit from treatment with a combination therapy with a RAF inhibitor and a second inhibitor is provided. A method of treating cancer in a subject in need thereof is also provided and includes administering to the subject an effective amount of a RAF inhibitor and an effective amount of a second inhibitor, wherein the second inhibitor is a MEK inhibitor, a CRAF inhibitor, a CrkL inhibitor or a TPL2 / COT inhibitor. A method of identifying a kinase target that confers resistance to a first inhibitor is also provided.

Provided herein are pharmaceutical compositions that include (a) a lipid nanoparticle comprising a protein kinase inhibitor (e.g., MEK inhibitor, PI3K inhibitor, or RAF inhibitor) and a chemotherapeutic agent; and (b) a hydrogel comprising a thermosensitive and biodegradable polymer. Also provided herein are methods of treating a cancer in a subject that include administering to the subject a therapeutically effective amount of any one of the pharmaceutical compositions described herein.

The invention discloses application of an AKT inhibitor or an STAT3 inhibitor in preparation of a medicine for overcoming drug resistance of bladder cancer to an MEK inhibitor, and belongs to the field of biological medicine. Detecting the cell activity through an MTT method; a Western blot experiment is adopted to detect a key target protein or gene expression level, a bladder cancer drug-resistant cell ERK abnormal activation + STAT3 / Akt compensation activation mechanism is defined, p-ERK, p-STAT3 and p-Akt are locked as targets, the drug resistance of bladder cancer to an MEK inhibitor is overcome through an AKT inhibitor or an STAT3 inhibitor, the scheme can accurately inhibit abnormal pathways, reverse drug resistance and improve treatment sensitivity, and the method is safe and suitable for clinical application. A new direction is provided for patients with drug-resistant bladder cancer, and the clinical bottleneck of the MEK inhibitor is helped to be broken through.

The present invention relates to a combination of a MEK inhibitor and Omomyc, a functionally equivalent variant thereof, a conjugate comprising Omomyc or said functionally equivalent variant, a polynucleotide encoding said polypeptide, a vector comprising said polynucleotide and a cell capable of secreting said polypeptide or said conjugate. The invention also relates to a pharmaceutical composition comprising a combination of the invention and its medical use, in particular its use in the treatment of cancer.

Disclosed herein are dosage forms comprising a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of: (a) at least one KRAS inhibitor; (b) at least one BRAF inhibitor; (c) at least one MEK inhibitor; (d) at least one mTOR inhibitor; or (e) any combination of (a)-(d). The dosage forms of the present disclosure can be used to treat subjects suffering from one or more cancers.

Provided herein are methods of using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing hematological malignancies. The second active agent is one or more of an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, a SUV420H1 / H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or a chemotherapy.

The application discloses a combination of a MEK inhibitor and a PLCbeta / PKC signal path inhibitor and application of the combination in treating BRAF(V600E) mutant tumors, and belongs to the field of biological medicines. The PLCbeta / PKC signal path inhibitor is combined with the MEK inhibitor, drug resistance can be reversed, stronger anti-BRAF(V600E) mutant tumor activity is exhibited, the growth of tumors can be more effectively inhibited, and the defects of poor treatment effect or large toxic side effects of single drug treatment are overcome. The application has a good application prospect.

The application belongs to the technical field of biological medicine, and particularly relates to application of an imidazoquinazoline small-molecule compound or a pharmaceutically acceptable salt thereof shown in formula (I) in preparation of a drug for treating KRAS mutant gastrointestinal tumors, wherein R is as described in the claims and the specification. The imidazoquinazoline compound can selectively inhibit proliferation, migration and invasion of KRAS mutant gastrointestinal tumor cells, and induce cell cycle arrest and apoptosis. Specifically, the compound exerts an anti-tumor effect by inhibiting the binding of p-ERK2 and p53, restoring p53 transcriptional activity, and up-regulating the expression of a pro-apoptotic gene PUMA downstream of p53. The mechanism of action is different from that of traditional KRAS or MEK inhibitors, and provides a new treatment option for KRAS mutant gastrointestinal tumor patients.