10 results about "HRAS" patented technology

Disclosed herein are compounds, and salts thereof, which inhibit targeted Ras mutants, pharmaceutical formulations, and methods of treatment of NRAS-, KRAS, or HRAS-mediated diseases, such as certain cancers.

This disclosure provides compounds of Formula (I) or (II) (e.g., Formula (II-a), (Il-b), or (II-c)), or pharmaceutically acceptable salts thereof, that inhibit a Ras GTPase (e.g., a KRas, NRas, and / or HRas GTPase). In some embodiments, the Ras protein is a dysregulated Ras protein that has a mutation (referred to herein as a mutant Ras protein). These compounds are useful, for example, for treating a disease, disorder, or condition in which increased and / or sustained (e.g., excessive) Ras activation, such as Ras activation associated with a mutant Ras protein, contributes to the pathology and / or symptoms and / or progression of the disease, disorder, or condition (e.g., cancer) in a subject (e.g., a human). This disclosure also provides compositions containing compounds of Formula (I) or (II) (e.g., Formula (II-a), (Il-b), or (II- c)), or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

The application discloses a method for detecting thyroid cancer driving gene mutations based on multiplex fluorescence PCR, and belongs to the technical field of molecular biology detection. The method simultaneously detects nine mutation sites, namely BRAF V600E, NRAS Q61R, NRAS Q61K, HRAS Q61R, HRAS Q61K, KRAS G12V, KRAS G12D, TERT C228T and TERT C250T in a single tube reaction. The method enhances the distinguishing ability of wild type and mutant types by using a locked nucleic acid modified allele-specific primer, suppresses wild type amplification by using a peptide nucleic acid clamp, introduces a competitive internal reference probe to correct amplification efficiency difference, and reduces the sample usage to one fifth of that of a traditional multi-tube scheme. The mutation detection lower limit reaches 0.5% allele frequency, and the total time consumption is not more than 2.5 h.

The application belongs to the field of biological medicine, and particularly relates to a group of gene mutations and application thereof in diagnosis of pancreaticobiliary duct cancer. Specifically, the application provides a group of gene mutations for detecting pancreaticobiliary duct cancer, wherein the gene mutations include one or more of AKT1, KRAS, APC, NRAS, ARID1A, PIK3CA, AXIN1, PPP2R1A, BAP1, PTEN, BRAF, SMAD4, CDKN2A, TERT, TP53, EGFR, FBXW7, FGFR2, HRAS, IDH1 and IDH2.

The present application relates to a kind of molecular marker for diagnosing cancer, kit and its application, belong to biotechnology field.The present application provides the m 6 A modification as a molecular marker for diagnosing cancer, the m 6 A modification site is A923, A930 and A955, 3 m 6 A modification site is regulated by demethylase FTO and ALKBH5, promotes HRAS protein expression and the proliferation and metastasis of cancer cell.The present application first identifies the epigenetic transcription modification of HRAS and clarifies relevant molecular mechanism, provides new single / combination targeting treatment theoretical basis for RAS this "difficult drug target".

The invention discloses application of an NASH-HCC mouse model, and belongs to the technical field of drug evaluation. The NASH-HCC mouse model can be applied to screening and / or evaluation of drugs and / or equipment for treating and / or preventing liver diseases, the NASH-HCC mouse model is an inducible Cre mouse, the HRAS protein is specifically and highly expressed in the liver under the induction of an inducer, and the liver diseases are NAFLD, NASH or HCC. The model can comprehensively evaluate the curative effect of a drug treatment scheme through multiple aspects such as mouse liver weight, blood biochemical indexes, total ROS (reactive oxygen species) amount of liver and spleen tissues, immune cell change conditions and the like, and provides support and assistance for clinical application.

This disclosure provides compounds of Formula ( I ) (e.g., Formula ( I-a )), ( II ), ( III ), or ( IV ), or pharmaceutically acceptable salts thereof, that inhibit a Ras GTPase (e.g., a KRas, NRas, and / or HRas GTPase). In some embodiments, the Ras protein is a dysregulated Ras protein that has a mutation (referred to herein as a mutant Ras protein). These compounds are useful, for example, for treating a disease, disorder, or condition in which increased and / or sustained (e.g., excessive) Ras activation, such as Ras activation associated with a mutant Ras protein, contributes to the pathology and / or symptoms and / or progression of the disease, disorder, or condition (e.g., cancer) in a subject (e.g., a human). This disclosure also provides compositions containing compounds of Formula ( I ) (e.g., Formula ( I-a )), ( II ), ( III ), or ( IV ), or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

This disclosure provides compounds of Formula (I), or pharmaceutically acceptable salts thereof, that inhibit a Ras GTPase (e.g., a KRas, NRas, and / or HRas GTPase). In some embodiments, the Ras protein is a dysregulated Ras protein that has a mutation (referred to herein as a mutant Ras protein). These compounds are useful, for example, for treating a disease, disorder, or condition in which increased and / or sustained (e.g., excessive) Ras activation, such as Ras activation associated with a mutant Ras protein, contributes to the pathology and / or symptoms and / or progression of the disease, disorder, or condition (e.g., cancer) in a subject (e.g., a human). This disclosure also provides compositions containing compounds of Formula (I) (e.g., Formula (I-a) or Formula (I-b)), or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

The invention discloses a construction method of an NASH-HCC mouse model, and belongs to the technical field of gene editing animal models. The construction method comprises the following steps: constructing a targeting vector containing a target sequence fragment of LoxP-Stop-LoxP-HRAS, transfecting the targeting vector into a mouse ES cell, injecting the targeting vector into a receptor embryo sac, transplanting an embryo to the uterus of a pseudopregnant mouse, screening out a chimeric mouse, mating the chimeric mouse with an inbred strain laboratory mouse to obtain a heterozygous mouse, selfing the heterozygous mouse to obtain a positive homozygous mouse, and screening the positive homozygous mouse to obtain the target sequence fragment of the LoxP-Stop-LoxP-HRAS. And mating a homozygote mouse with an inducible Cre mouse to obtain a double-heterozygous NASH-HCC mouse model containing the gene sequence of the targeting vector and the inducible Cre sequence, thereby obtaining the double-heterozygous NASH-HCC mouse model. The NASH-HCC mouse model has the advantages of typical clinical characteristics, controllable disease process, high morbidity and the like.

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.