30 results about "BRAF inhibitor" patented technology

The present invention provides a preparation method for a BRAF inhibitor (formula (A). The method involves mild reaction conditions, simple operations, high reaction yield, high product purity and convenient post-treatment, and thus is suitable for industrial production.

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 invention provides application of an intracellular lactic acid level increasing agent in preparation of a drug for enhancing sensitivity of BRAF V600E mutant tumors to a BRAF inhibitor or in preparation of a drug for treating BRAF V600E mutant tumors resistant to the BRAF inhibitor. According to the invention, the intracellular lactic acid concentration is improved by using an intracellular lactic acid level improver, SUMOylation of BRAFV600E protein is promoted, and the BRAFV600E protein is locked in an open drug sensitive conformation; in-vivo and in-vitro experiments prove that the combination of the MCT4 inhibitor and the BRAF inhibitor (such as vimofenib) has a remarkable synergistic anti-tumor effect, drug resistance can be effectively relieved, and a new treatment strategy is provided for refractory colorectal cancer and the like.

The application relates to the field of biomedical technology, and discloses a diagnostic agent for identifying melanoma molecular subtype typing and application, wherein the diagnostic agent comprises a first antibody specifically combined with a SOX10 protein and a second antibody specifically combined with an EGR1 protein; the diagnostic agent can be applied to preparation of a diagnostic product for evaluating the prognostic effect of a melanoma patient, preparation of a diagnostic product for predicting the treatment sensitivity of melanoma to a BRAF inhibitor, and preparation of a diagnostic product for guiding an individualized treatment scheme of melanoma. The diagnostic agent for melanoma molecular subtype typing can be directly transformed into clinical practice, and can assist in realizing real individualized treatment.

The present invention relates to a pharmaceutical composition or a pharmaceutical preparation. The pharmaceutical composition or the pharmaceutical preparation comprises a therapeutically effective amount of an active ingredient M and a pharmaceutically acceptable excipient, wherein the active ingredient M is selected from a compound as shown in general formula I or a stereoisomer, tautomer, deuterated product, solvate, prodrug, metabolite, pharmaceutically acceptable salt or eutectic crystal thereof, and the pharmaceutical composition or the pharmaceutical preparation comprises 1-1000 mg of the active ingredient M. The present invention also relates to a use of the pharmaceutical composition or the pharmaceutical preparation in preparation of a related drug for treating cancers.

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.

This application provides amorphous solid dispersions of Compound I and their uses.

The present invention relates to combination therapies of a BRAF inhibitor and an ALK / TRK inhibitor, or their pharmaceutically acceptable salts, hydrates, or solvates thereof, and their use in the treatment of cancer, in particular colorectal cancer, including BRAF mutant colorectal cancer. Methods of treatment and methods of predicting whether a subject having colorectal cancer is likely to respond to treatment are also disclosed herein.

The application discloses combination therapies using a combination of a WEE1 inhibitor and a BRAF inhibitor, and optionally an EGFR inhibitor, for the treatment of diseases, such as colorectal cancer.

The present invention provides the use of the combination of an HSPA8 inhibitor and a BRAF inhibitor in the preparation of a medicament for treating colorectal cancer. Experimental evidence of the present invention shows that high expression of HSPA8 can serve as a biological marker for poor prognosis of BRAF V600E colorectal cancer; HSPA8 degrades CAV1 through the CMA pathway, releases β-catenin into the nucleus, and activates the Wnt pathway; HSPA8 binds to the KISFN motif of CAV1, and phosphorylation of CAV1 S168 mediated by p38MAPK can promote their interaction; the combined use of an HSPA8 inhibitor and a BRAF V600E-targeted drug can significantly enhance the tumor suppression effect.

A pharmacological agent and method for treatment of cancer and vascular-related disorders of skin and colon are described. The pharmacological agent, which is a small molecule that targets and inhibits both RhoJ and CDC42 signaling, demonstrates potent anti-vascular effects in normal skin, colon, and tumors, combined with low toxicity, especially as compared to BRAF inhibitors (such as, vemurafenib used in melanoma treatments), selective CDC42 inhibitors (such as CASIN), and VEGF inhibitors (known as anti-vascular agents, such as, for example, linifanib). As such, the pharmacological agent is particularly suited for applications related to treating cancer, as well as disorders of the skin and colon that exhibit increased vasculature.

The present invention relates to a bicyclic-type MAT2A inhibitor and use thereof. Specifically, the present invention discloses a bicyclic compound represented by formula (I) or a pharmaceutically acceptable salt, an enantiomer, a diastereomer, a racemate, an atropisomer, a polymorph, a solvate, or an isotope labeled compound thereof. The compound represented by formula (I) has MAT2A enzyme inhibitory activity, can be used as a good MAT2A inhibitor, and is further used for preparing drugs for treating and / or preventing MTAP-related diseases, especially tumors.

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.

The invention relates to the technical field of biomedicine, and discloses a diagnostic agent for identifying melanoma molecular subtype typing and application, the diagnostic agent comprises a first antibody specifically binding to SOX10 protein and a second antibody specifically binding to EGR1 protein, the diagnostic agent can be applied to preparation of a diagnostic product for evaluating the prognosis effect of a melanoma patient, preparation of a diagnostic product for predicting the treatment sensitivity of melanoma to a BRAF inhibitor, and preparation of a diagnostic product for guiding an individualized treatment scheme of melanoma. The diagnostic agent for melanoma molecular subtype typing can be directly converted into clinical practice, and real individualized treatment can be achieved in an auxiliary mode.

The EphA2 targeting agents developed herein are potent peptidomimetics having a high affinity (Kd 8-20 nanomole) to the ligand binding domain referred to as tagfolin. Monomeric versions of tagfolin act as antagonists, while dimeric versions of said agents (tagfolin dimers) result in internalization and degradation of receptors via lysosomal pathways. Thus, when used as a single agent or in combination with a standard care, the tagfolin dimer agent is effective in reducing cancerogenic EphA2 levels in cancer cells. Tagfolin dimers may also sensitize cancer cells that are resistant to EGFR or BRAF inhibitors and potentially other anti-cancer agents. Furthermore, the dimeric agent can be conjugated to a chemotherapeutic agent, such as paclitaxel, to selectively deliver a cytotoxic agent to the EphA2-expressing cancer cells. The monomeric agent can be linked to the chemotherapeutic agent via a stable cleavable linker, causing the cytotoxic to accumulate at the tumor, which then enters the tumor. Novel compositions and examples of these applications are reported.

The description provides compositions and methods for treating ETBR-related cancer. In certain aspects, the description provides a delivery system for the controlled, systemic release of at least one of ETBR antagonists, caspase-8 inhibitors, or a combination thereof, optionally including an ETAR antagonist, an anti-PD-1 antibody, a bRAF inhibitor, niacinamide or a combination thereof. The compositions described are useful for the treatment of certain cancers, including, e.g., breast cancer, malignant melanoma, squamous cell carcinoma, glioblastoma, as well as others. In addition, the description provides a delivery system for the controlled release of at least one of ETBR antagonists, caspase-8 inhibitors or a combination thereof, optionally including at least one of an ETAR antagonist, an anti-PD-1 antibody, a bRAF inhibitor, niacinamide, or a combination thereof, to the central nervous system that are useful for treating cancers that have spread to the brain.

Methods for predicting the therapeutic response of a cancer in a patient and / or for identifying a treatment for a patient who has been diagnosed as having or being likely to have cancer are described, comprising detecting the presence of one or more specific mitogen pathway protein variants in cancer cells of the patient, wherein the presence of the one or more mitogen pathway protein variants are indicative of response to one or more of: MAP2K1 / 2 inhibitors, BRAF inhibitors, EGFR inhibitors, PI3K inhibitors, and KRAS inhibitors Related methods and products are also described.

The present invention relates to combinations of an AR inhibitor and one or more MAPK signalling inhibitor(s) like BRAF inhibitor and / or MEK inhibitors and the use of said combinations for the treatment or prophylaxis of diseases, in particular of skin melanoma, as a sole combination or in combination with other active ingredients.

Provided herein are combination therapies comprising a BRAF inhibitor (e.g., a compound of formula (I) or a pharmaceutically acceptable salt thereof) and an EGFR inhibitor (EGFRi), as well as pharmaceutical compositions, methods, and uses of the combination therapies.

The description provides compositions and methods for treating ETBR-related cancer. In certain aspects, the description provides a delivery system for the controlled, systemic release of at least one of ETBR antagonists, caspase-8 inhibitors, or a combination thereof, optionally including an ETAR antagonist, an anti-PD-1 antibody, a bRAF inhibitor, niacinamide or a combination thereof. The compositions described are useful for the treatment of certain cancers, including, e.g., breast cancer, malignant melanoma, squamous cell carcinoma, glioblastoma, as well as others. In addition, the description provides a delivery system for the controlled release of at least one of ETBR antagonists, caspase-8 inhibitors or a combination thereof, optionally including at least one of an ETAR antagonist, an anti-PD-1 antibody, a bRAF inhibitor, niacinamide, or a combination thereof, to the central nervous system that are useful for treating cancers that have spread to the brain.

The present invention relates to a combination of a BRAF 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.

The expression of the P-glycoprotein (P-gp) efflux transporter at the blood-brain interface impedes BBB penetrance of most small molecules. Designing efflux liabilities out of compounds can be laborious and there is no generalizable approach to transform periphery-limited agents to ones active in the CNS. A target-agnostic, prospective assessment of P-gp efflux using diverse compounds indicated a reduction in molecular size or appending a carboxylic acid that enabled evasion of P-gp efflux in cell-based experiments and in mice. Such strategy was applied to transform a periphery-limited V600EBRAF inhibitor, dabrafenib, into compounds that possess potent and selective anti-cancer activity, but now also evaded P-gp-mediated efflux. When compared to dabrafenib, the compound developed herein (everafenib) has superior BBB penetrance and superior efficacy in an intracranial mouse model of metastatic melanoma, suggesting it as a lead candidate for the treatment of melanoma metastases to the brain and gliomas with BRAF mutation.

Pharmaceutical topical compositions comprising compound of Formula IV and method of using pharmaceutical topical compositions comprising compound of Formula IV for the treatment or prevention of EGFR inhibitor, PI3K inhibitor, MEK inhibitor and / or HER dimerization inhibitor-induced acneiform lesions in a subject in need thereof are provided.

The invention relates to a combination of a BRAF inhibitor with Omomyc, a functionally equivalent variant thereof, a conjugate comprising Omomyc or said functionally equivalent variant, a polynucleotide encoding said polypeptides, a vector comprising said polynucleotide and a cell capable of secreting the polypeptide or the conjugate. The invention also relates to pharmaceutical compositions containing the combination of the invention and to their medical uses, particularly their uses in the treatment of cancer.

The present invention relates to a method for predicting the development of resistance to a BRAF inhibitor, alone or in combination with a MEK inhibitor (i.e., a MAPK pathway inhibitor or simply MAPKi), during anti-tumor therapy, said method comprising measuring the expression of both microRNAs miR-579-3p and miR-4488 in a biological sample collected from a tumor patient prior to the initiation of anti-tumor therapy with said MAPK pathway inhibitor, and determining the expression ratio of miR-4488 to miR-579-3p.

Provided herein are combination therapies comprising a BRAF inhibitor (e.g., a compound of formula (I), or a pharmaceutically acceptable salt thereof) and FOLFOX or FOLFIRI chemotherapy, as well as methods and uses thereof.

The present invention is directed to (3R)—N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide or a pharmaceutically acceptable salt thereof, for novel uses in the treatment of locally advanced solid tumours, in particular melanoma with brain metastases. The present invention also relates to pharmaceutical composition comprising (3R)—N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide or a pharmaceutically acceptable salt thereof.

Inhibitory peptides for modifying RAF kinase protein dimerization are described. The peptides display a binding affinity for the dimer interface of a B-Raf, allowing for modification of RAF kinase dimerization, and inhibition of tumor growth. An embodiment of the disclosure is a peptide generated by modifying SEQ ID NO: 1, which corresponds to amino acids 503-521 of B-Raf kinase, e.g., cyclization, N-terminal capping, C-terminal capping, substitution of one or more amino acid residues, etc. The peptides disclosed herein include a modification to SEQ ID NO: 1 that can improve or otherwise alter binding affinity of the peptide to the dimer interface.

The invention discloses a medication auxiliary system for tumor treatment and a pharmaceutical composition. The tumor treatment medication auxiliary system provided by the embodiment of the invention comprises a marker acquisition module used for acquiring a tumor marker of a patient; the medication suggestion module is used for giving corresponding medication suggestions based on the obtained tumor markers; the medication suggestion comprises the following steps: if the tumor marker contains BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT, recommending an inhibitor which is sensitive to a tumor carrying a triple gene combination of the BRAF V600E mutation, the TERT promoter mutation and the SNP rs2853669TT; the inhibitors comprise a BRAF inhibitor, an MEK inhibitor, an MYC inhibitor, an RAS inhibitor and a PI3K / AKT inhibitor. Expression of BRAF, MEK, MYC, RAS, PI3K / AKT and the like is specifically inhibited, and wide killing on normal cells is avoided. The high specificity improves the selectivity and safety of treatment, and reduces the side effects caused by traditional chemotherapy and radiotherapy.

The present invention relates to (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide or a pharmaceutically acceptable salt thereof for novel use in the treatment of locally advanced solid tumors, particularly melanoma with brain metastases. The present invention also relates to a pharmaceutical composition comprising (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide or a pharmaceutically acceptable salt thereof.