25 results about "RAS Mutation" patented technology

The present disclosure relates to antibody-drug conjugates, and more particularly to antibody-drug conjugates (ADCs) loaded with inhibitors of Ras mutations as well as compositions containing the ADC molecules and therapeutic applications thereof.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as a medicament, in particular for use in treating proliferative disorders, inflammatory diseases and / or genetic disorders. The present invention relates further to a pharmaceutical composition comprising the compounds of formula (I). Moreover, the present invention relates to a method of inhibiting growth, proliferation or metastasis of cancer cells in a subject in need thereof, in particular which may encompass subsets of patients defined by their mutational status of the RAS oncogene or patients who might have developed resistance to the standard of care or treatment with RAS mutation specific inhibitors. The present invention also relates to a method of inhibiting RAS molecules in treating genetic disorders like RASopathies or inflammatory disorders like Adenomyosis where KRAS gene is mutationally activated. In addition, the present invention relates to a method of inhibiting proliferation and or secretion of factors from a cell population sensitive towards inhibiting RAS activation in vitro, in particular sensitive towards inhibiting KRAS. HRAS and NRAS activation in vitro. Furthermore, the present invention relates to a kit containing a formulation comprising a pharmaceutical composition comprising a compound of formula (I).

The present invention relates to an antibody-drug conjugate, and in particular, to an antibody-drug conjugate (ADC) carrying a Ras mutation inhibitor, a composition comprising the ADC molecule, and therapeutic use thereof.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as a medicament, in particular for use in treating proliferative disorders, inflammatory diseases and / or genetic disorders. The present invention relates further to a pharmaceutical composition comprising the compounds of formula (I). Moreover, the present invention relates to a method of inhibiting growth, proliferation or metastasis of cancer cells in a subject in need thereof, in particular which may encompass subsets of patients defined by their mutational status of the RAS oncogene or patients who might have developed resistance to the standard of care or treatment with RAS mutation specific inhibitors. The present invention also relates to a method of inhibiting RAS molecules in treating genetic disorders like RASopathies or inflammatory disorders like Adenomyosis where KRAS gene is mutationally activated. In addition, the present invention relates to a method of inhibiting proliferation and / or secretion of factors from a cell population sensitive towards inhibiting RAS activation in vitro, in particular sensitive towards inhibiting KRAS, HRAS and NRAS activation in vitro. Furthermore, the present invention relates to a kit containing a formulation comprising a pharmaceutical composition comprising a compound of formula (I).

The present invention discloses nitrogen-containing macrocyclic compounds, pharmaceutical composition and use thereof. The present invention provides a compound represented by formula 0, a solvate, a pharmaceutically acceptable salt thereof or a solvate of the pharmaceutically acceptable salt thereof. The compounds of the present disclosure are orally bioavailable pan-RAS inhibitors which can target a wider range of RAS mutations than traditional mutant-selective RAS inhibitors, and have high exposure, long half-life and good pharmacokinetic properties, may be useful for the treatment of RAS-driven cancers and effective in patients who have not responded to other therapies.

To provide a method and system for supporting the determination of eligibility of conversion surgery (CS), which is radical resection after aggressive preoperative chemotherapy, for colorectal liver metastases, thereby solving the problem in which involvement of multiple factors make it difficult to determine whether the CS is feasible.SOLUTION: A method for supporting the determination of CS eligibility is provided by, at the initial diagnosis, examining and scoring the presence / absence of RAS mutations, the presence / absence of conservable segments, the number of tumors, and tumor contact with hepatic veins.SELECTED DRAWING: Figure 3A

The invention relates to a PI4K inhibitor and application thereof, in particular to application in blocking or inhibiting autophagy caused by RAS mutation or treating RAS mutation tumors. In addition, the invention discloses that the mechanism of the autophagy caused by RAS mutation is completely different from that of the existing starvation-induced autophagy, the pathway of the autophagy caused by RAS mutation is P38-ULK1-PI4KB-WIPI2, especially S256 and T263 sites of P14KB phosphorylated by ULK1, and experiments prove that the specificity of the pathway can be used as a diagnostic marker and a therapeutic target of tumors.

The present disclosure relates to an antibody-drug conjugate, and in particular, to an antibody-drug conjugate (ADC) loaded with an Ras mutation inhibitor, a composition comprising the ADC molecule, and therapeutic use thereof.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as a medicament, in particular for use in treating proliferative disorders, inflammatory diseases and / or genetic disorders. The present invention relates further to a pharmaceutical composition comprising the compounds of formula (I). Moreover, the present invention relates to a method of inhibiting growth, proliferation or metastasis of cancer cells in a subject in need thereof, in particular which may encompass subsets of patients defined by their mutational status of the RAS oncogene or patients who might have developed resistance to the standard of care or treatment with RAS mutation specific inhibitors. The present invention also relates to a method of inhibiting RAS molecules in treating genetic disorders like RASopathies or inflammatory disorders like Adenomyosis where KRAS gene is mutationally activated. In addition, the present invention relates to a method of inhibiting proliferation and / or secretion of factors from a cell population sensitive towards inhibiting RAS activation in vitro, in particular sensitive towards inhibiting KRAS, HRAS and NRAS activation in vitro. Furthermore, the present invention relates to a kit containing a formulation comprising a pharmaceutical composition comprising a compound of formula (I).

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as a medicament, in particular for use in treating proliferative disorders inflammatory diseases and / or genetic disorders. The present invention relates further to a pharmaceutical composition comprising the compounds of formula (I). Moreover, the present invention relates to a method of inhibiting growth, proliferation or metastasis of cancer cells in a subject in need thereof, in particular which may encompass subsets of patients defined by their mutational status of the RAS oncogene or patients who might have developed resistance to the standard of care or treatment with RAS mutation specific inhibitors. The present invention also relates to a method of inhibiting RAS molecules in treating genetic disorders like RASopathies or inflammatory disorders like Adenomyosis where KRAS gene is mutationally activated. In addition, the present invention relates to a method of inhibiting proliferation and or secretion of factors from a cell population sensitive towards inhibiting RAS activation in vitro, in particular sensitive towards inhibiting KRAS, HRAS and NRAS activation in vitro. Furthermore, the present invention relates to a kit containing a formulation comprising a pharmaceutical composition comprising a compound of formula (I).

In accordance with the purpose(s) of the present disclosure, described herein are methods for treating cancer associated with a Ras mutation in a subject in need of treatment comprising administering to the subject an effective amount of a compound of formula I as described herein or a pharmaceutically acceptable salt thereof. The compounds described herein have improved efficacy compared to the benchmark BET inhibitor JQ-1 and comparable efficacy to high dose JQ-1 with respect to the treatment of PDAC. In one aspect, the compounds are administered in combination with an effective amount of an immune checkpoint inhibitor such as, for example, PD-1 / PD-L 1 inhibitor, a CTLA-4 inhibitor, or a combination thereof.

The present application provides anucleate cells comprising a mutated Ras antigen (such as a mutated K-Ras antigen), methods of manufacturing such anucleate cells comprising the mutated Ras antigen, and methods of using such modified anucleate cells for stimulating an immune response, treating, and / or vaccinating an individual with a cancer associated with Ras mutation.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as medicaments, in particular for the treatment of proliferative disorders, inflammatory diseases and / or genetic disorders. The invention also relates to a pharmaceutical composition comprising the compound of formula (I). Furthermore, the present invention relates to methods of inhibiting the growth, proliferation or metastasis of cancer cells in an individual in need thereof, in particular, which may include a subpopulation of patients defined by RAS oncogene mutation status or patients who may be resistant to care or treatment criteria for RAS mutation-specific inhibitors. The invention also relates to methods of treating genetic disorders such as RAS disease or inflammatory disorders such as adenomyosis by inhibiting RAS molecules, wherein the KRAS gene is mutated and activated. Furthermore, the present invention relates to methods of inhibiting cell population proliferation and / or factor secretion that are sensitive in vitro to inhibition of RAS activation, in particular to inhibition of KRAS, HRAS and NRAS activation in vitro. Furthermore, the present invention relates to a kit comprising a formulation comprising a pharmaceutical composition comprising the compound of formula (I). # imgabs0 #

The present invention relates to an antibody-drug conjugate, and in particular, to an antibody-drug conjugate (ADC) carrying a Ras mutation inhibitor, a composition comprising the ADC molecule, and therapeutic use thereof.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as pharmaceutical agents, particularly for the treatment of proliferative, inflammatory, and / or genetic disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of formula (I). Furthermore, the present invention relates to methods for inhibiting the growth, proliferation, or metastasis of cancer cells in a subject in need thereof, which may include, in particular, a subset of patients defined by their RAS oncogene mutation status, or patients who have developed resistance to standard treatment or treatment with RAS mutation-specific inhibitors. The present invention also relates to methods for inhibiting RAS molecules in the treatment of genetic disorders such as RAS syndromes or inflammatory diseases such as adenomyosis in which the KRAS gene is activated by mutations. The present invention also relates to methods for inhibiting the proliferation and / or secretion of factors from cell populations sensitive to in vitro inhibition of RAS activation, particularly cell populations sensitive to in vitro inhibition of KRAS, HRAS, and NRAS activation. Furthermore, the present invention relates to kits containing formulations of pharmaceutical compositions containing compounds of formula (I).

The invention relates to a mixture comprising at least one compound (I) and at least one compound (II). The present invention also relates to a method of inhibiting cancer cell growth, proliferation or metastasis in a subject in need thereof, the subject including, inter alia, a patient defined by the mutation status of the RAS oncogene or a subset of patients likely to produce resistance to standard care or treatment of RAS mutation-specific inhibitors. In addition, the invention relates to a pharmaceutical composition and its use in the prevention and / or treatment of proliferative diseases. Furthermore, the present invention relates to a kit comprising a formulation comprising the pharmaceutical composition comprising the mixture.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as medicaments, in particular for the treatment of proliferative disorders, inflammatory diseases and / or genetic disorders. The invention also relates to a pharmaceutical composition comprising the compound of formula (I). Furthermore, the present invention relates to methods of inhibiting the growth, proliferation or metastasis of cancer cells in an individual in need thereof, in particular, which may include a subpopulation of patients defined by RAS oncogene mutation status or patients who may be resistant to care or treatment criteria for RAS mutation-specific inhibitors. The invention also relates to methods of treating genetic disorders such as RAS disease or inflammatory disorders such as adenomyosis by inhibiting RAS molecules, wherein the KRAS gene is mutated and activated. Furthermore, the present invention relates to methods of inhibiting cell population proliferation and / or factor secretion that are sensitive in vitro to inhibition of RAS activation, in particular to inhibition of KRAS, HRAS and NRAS activation in vitro. Furthermore, the present invention relates to a kit comprising a formulation comprising a pharmaceutical composition comprising the compound of formula (I).

The presently disclosed subject matter provides novel T cell receptors (TCRs) that target a mutated RAS protooncogene. The presently disclosed subject matter further provides cells comprising such TCRs, and methods of using such cells for treating cancers associated with RAS.

The invention provides a RAF inhibitor and a MEK inhibitor for combined use in the treatment of a solid tumor, and is based on identifying certain RAS mutations, a method for identifying a patient suffering from a solid tumor for amenability to combined treatment with a RAF inhibitor and a MEK inhibitor, a corresponding method of treatment and related invention aspects or embodiments as described in detail below. The RAS mutations are in codon Q61 or a G13R mutation.

A PI4K inhibitor and use thereof, especially use in blocking or inhibiting autophagy caused by RAS mutations or treating tumors associated with RAS mutations. In addition, the present invention reveals that autophagy caused by RAS mutations is completely different in mechanism from existing starvation-induced autophagy. The pathway of autophagy caused by RAS mutations is P38-ULK1-PI4KB-WIPI2, especially the S256 and T263 sites of ULK1 phosphorylated PI4KB. It has been experimentally confirmed that the specificity of the pathway can be used as a diagnostic marker and a therapeutic target of tumors.

This disclosure relates to antibody-drug conjugates, and more specifically to antibody-drug conjugates (ADCs) carrying Ras mutation inhibitors, compositions containing said ADC molecules, and their therapeutic applications.

This invention discloses nitrogen-containing macrocyclic compounds, pharmaceutical compositions thereof, and uses. The invention provides compounds represented by Formula 0, their solvates, pharmaceutically acceptable salts thereof, or solvates of pharmaceutically acceptable salts thereof. The disclosed compounds are pan-RAS inhibitors with oral bioavailability, targeting a wider range of RAS mutations compared to conventional mutation-selective RAS inhibitors. They exhibit high exposure, long half-life, and favorable pharmacokinetic properties, and can be used to treat RAS-driven cancers, showing efficacy in patients unresponsive to other therapies.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as a medicament, in particular for use in treating proliferative disorders, inflammatory diseases and / or genetic disorders and / or genetic disorders. The present invention relates further to a pharmaceutical composition comprising the compounds of formula (I). Moreover, the present invention relates to a method of inhibiting growth, proliferation or metastasis of cancer cells in a subject in need thereof, in particular which may encompass subsets of patients defined by their mutational status of the RAS oncogene or patients who might have developed resistance to the standard of care or treatment with RAS mutation specific inhibitors. The present invention also relates to a method of inhibiting RAS molecules in treating genetic disorders like RASopathies or inflammatory disorders like Adenomyosis where KRAS gene is mutationally activated. In addition, the present invention relates to a method of inhibiting proliferation and / or secretion of factors from a cell population sensitive towards inhibiting RAS activation in vitro, in particular sensitive towards inhibiting KRAS, HRAS and NRAS activation in vitro. Furthermore, the present invention relates to a kit containing a formulation comprising a pharmaceutical composition comprising a compound of formula (I).

This invention provides cyclic compounds effective against RAS-mutated cancers, as well as non-natural amino acids and peptide compounds useful for their production, particularly peptide compounds that exhibit sufficiently selective KRAS inhibitory activity against HRAS and NRAS. [Solution] The present invention provides a cyclic compound having a specific amino acid sequence that interacts with and selectively inhibits amino acid residues specific to KRAS, or a salt thereof, or a solvate thereof. The pharmacological effect of the cyclic compound is to inhibit the proliferation of tumor cells having RAS mutations.

The present application provides nucleated cells comprising a mutated Ras antigen (such as a mutated K-Ras antigen), methods of manufacturing such nucleated cells comprising the mutated Ras antigen, and methods of using such modified nucleated cells (e.g., immune cells) for stimulating an immune response, treating, and / or vaccinating an individual with a cancer associated with Ras mutation.