204 results about "KRAS" patented technology

The present disclosure relates to an improved, efficient, scalable process to prepare intermediate compounds, such as 2-isopropyl-4-methylpyridin-3-amine, useful for the synthesis of compounds, such as Compound 9, for the treatment of KRAS G12C mutated cancers.

A multi-targeted siRNA for treating cancers is disclosed. Specifically, an siRNA composition is provided, comprising: a first siRNA molecule that reduces the expression of the first target gene; optionally, a coding sequence targeting a peptide element; and optionally, a second siRNA molecule that reduces the expression of the second target gene, wherein the first target gene is selected from the group consisting of EGFR, KRAS, or a combination thereof, and the siRNA composition reduces the expression of two or more genes. The siRNA or vector provided can be directly injected into the body to treat cancers.

A compound represented by formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition thereof, a preparation method therefor, and a use thereof. The compound has one or more of the following effects: (1) good KRAS G12C inhibitory activity; (2) good KRAS G12D inhibitory activity; (3) good KRAS G12V inhibitory activity; (4) optimal exposure dose; (5) good bioavailability; and (6) good in vivo efficacy.

of KRAS G12C mutated cancers. O N F oH N N N N F O M iPr N 20 26 20 48 47 23 J un 2 02 6 A B S T R A C T 2 0 2 6 2 0 4 8 4 7 2 3 J u n 2 0 2 6 o f K R A S G 1 2 C m u t a t e d c a n c e r s . 0 N F O H N N N N F N

The invention discloses a novel pyrimidine KRAS-G12C inhibitor as well as a preparation method and application of the novel pyrimidine KRAS-G12C inhibitor. The pyrimidine compound disclosed by the invention has a remarkable inhibition effect on non-small cell lung cancer cells (NCI-H23 and NCI-H358) with high expression of KRAS-G12C, is particularly used as a medicine for treating and / or preventing the non-small cell lung cancer, is simple and efficient in preparation route, and has a good antitumor medicine development and application prospect.

Provided is a compound useful as an active ingredient in a pharmaceutical composition for treating cancer.　The present inventors have examined a compound useful as an active ingredient in a pharmaceutical composition for cancer treatment, and have completed the present invention by finding that: a heterocyclic compound represented by formula (I) and formula (I-I) has excellent an action of inducing degradation of a mutant KRAS protein and a wild-type KRAS protein, and in particular, an action of inducing degradation of a KRAS protein having a G12C mutation, G12D mutation, G12V mutation, or G13D mutation; and said heterocyclic compound has mutant KRAS inhibition and the inhibitory activity of KRAS amplified by a wild-type KRAS gene, and in particular, inhibitory activity of KRAS having a G12C mutation, G12D mutation, G12V mutation, or G13D mutation. The heterocyclic compound according to the present invention or a salt thereof can be used as a therapeutic agent for cancer.

The application discloses a five-heterocycle compound, a preparation method and application thereof. Specifically disclosed are a compound as shown in formula I, a pharmaceutically acceptable salt or solvate thereof, a composition containing the compound, and a pharmaceutical use of the compound for preparing a drug for treating a disease or disorder related to the mechanism of action of KRAS G12C mutant protein. The five-heterocycle compound in the application has the activity of inhibiting the proliferation of Ba / F3 KRAS-G12C cells, NCI-H358 cells and MIA PaCa-2 cells expressing KRAS G12C mutant protein, and has a good inhibitory effect on the growth of a subcutaneous transplanted tumor of a NCI-H358 nude mouse.

Provided herein are compounds, or salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers thereof, as well as pharmaceutical compositions comprising the same. Also provided herein are methods of using the same in modulating (e g., inhibiting) KRAS (e.g., KRAS having a G12D mutation) and treating diseases or disorders such as cancers in subjects in need thereof.

Provided herein are compounds of Formula (II) (e.g., Formula (II-a), (II-b), (II-a1), (II-b1), (II-a2), (II-b2), (II-3), (II-a3), (II-4), (II-a4), (II-5), (II-a5), (II-6), (II-a6), (II-7), (II-a7), (II-7), or (II-a8)), Formula (III) (e.g., Formula (III-1), (III-2), (III-3), (III-4), (III-5), (III-6), (III-7), or (III-8)), Formula (IV) (e.g., Formula (IV-a), (IV-b), (IV-c), (IV-a1), (IV-b1), (IV-a2), (IV-b2), (IV-a3), (IV-b3), (IV-a4), (IV-b4), (IV-a5), (IV-b5), (IV-a6), (IV-b6), (IV-a7), (IV-b7), (IV-a8), or (IV-b8)), Formula (V) (e.g., Formula (V-a) or (V-b), (V-a1), (V-c), (V-d), (V-b1), (V-a2), (V-b2), (V-a3), or (V-b3)), Formula (VI) (e.g., Formula (VI-a), (VI-b), (VI-c), (VI-d), or (VI-e))), or Formula (A) (e.g., Formula (I-a1)), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein (e.g., a dysregulated KRas protein (e.g., a mutated or amplified KRas protein)). This disclosure also provides compositions containing the compounds as provided herein, or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

Pharmaceutical compositions and therapeutic methods are provided comprising a single-domain antibody consisting of SEQ ID NO:1 and a pharmaceutically acceptable carrier. The antibody inhibits KRAS GTPase activity and inhibits phosphorylation of STAT3. In certain embodiments, inhibition of KRAS results in decreased phosphorylation of ERK1 / 2. The antibody reduces tumor cell surface PD-L1 expression and reduces VEGF production. The antibody crosses the blood-brain barrier following systemic administration and may exhibit sustained biological activity in vivo. Methods are provided for treating KRAS-mutant cancers, including pancreatic cancer and triple negative breast cancer, and for enhancing anti-tumor immunity through reduction of PD-L1 expression.

The application discloses an inhibitor for inhibiting KRAS phase separation to play an anti-tumor role and application, and relates to the fields of tumor molecular biology and targeted therapy.The application aims at solving the problems of limited effect, strong drug resistance and limited application range of KRAS tumor treatment methods, and the inhibitor is a statin.The KRAS protein can form a liquid condensate in cells, and the application discloses the mechanism of the KRAS protein in promoting KRAS protein processing, transportation and downstream signal activation, and further provides a technical scheme for inhibiting tumor growth and enhancing the therapeutic effect of a KRAS inhibitor by inhibiting the formation of KRAS condensates, so as to provide a new target and intervention approach for tumor treatment.

Provided herein are compounds of Formula (II) (e.g., Formula (II-a), (II-b), (II-a1), (II-b1), (II-a2), (II-b2), (II-3), (II-a3), (II-4), (II-a4), (II-5), (II-a5), (II-6), (II-a6), (II-7), (II-a7), (II-7), or (II-a8)), Formula (III) (e.g., Formula (III-1), (III-2), (III-3), (III-4), (III-5), (III-6), (III-7), or (III-8)), Formula (IV) (e.g., Formula (IV-a), (IV-b), (IV-c), (IV-a1), (IV-b1), (IV-a2), (IV-b2), (IV-a3), (IV-b3), (IV-a4), (IV-b4), (IV-a5), (IV-b5), (IV-a6), (IV-b6), (IV-a7), (IV-b7), (IV-a8), or (IV-b8)), Formula (V) (e.g., Formula (V-a) or (V-b), (V-a1), (V-c), (V-d), (V-b1), (V-a2), (V-b2), (V-a3), or (V-b3)), Formula (VI) (e.g., Formula (VI-a), (VI-b), (VI-c), (VI-d), or (VI-e))), or Formula (A) (e.g., Formula (I-a1)), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein (e.g., a dysregulated KRas protein (e.g., a mutated or amplified KRas protein)). This disclosure also provides compositions containing the compounds as provided herein, or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

The invention relates to cancer biology, more specifically to the treatment of KRAS mutant cancers. A potent cancer therapy is provided by the combination of a farnesyl transferase inhibitor compound and a KRAS inhibitor compound.

A pharmaceutical combination including a Raf inhibitor which is Compound of formula (I) or a pharmaceutically acceptable salt thereof, (b) a KRAS G12C inhibitor, and / or (c) trametinib.

Described herein are methods for treating cancer in a patient, the methods comprising administering to the patient a PRMT5 inhibitor and a PARP inhibitor, a KRAS inhibitor, or a kinase-like protein 18A (KIF18A) inhibitor, or a kinase inhibitor.

Provided herein are KRAS proteolytic targeting chimeras (PROTACs), compositions comprising the KRAS PROTACs, and methods of making and using the KRAS PROTACs, for example, to promote degradation of KRAS and / or to treat KRAS-related cancers. In embodiments, KRAS PROTAC has the structural formula: or a pharmaceutically acceptable salt thereof, where the values of the variables (e.g., ring A, X4, Y, R2, R3, R4, L ', Detron) are as described herein.

This invention discloses an enhanced TCR and its uses. The enhanced TCR includes an α-chain variable region containing CDR1α, CDR2α, and CDR3α, and a β-chain variable region containing CDR1β, CDR2β, and CDR3β; wherein the enhanced TCR has a T30H mutation relative to the parental TCR's CDR1α, or the enhanced TCR has an S102H or G99H mutation relative to the parental TCR's CDR3α. The enhanced TCR provided by this invention is obtained by mutation based on the parental TCR, possessing a highly sensitive ability to bind target antigen peptides, significantly improving target cell recognition ability, and mediating the specific killing effect of effector cells on antigen-positive target cells, and exhibiting no allogeneic reaction to different HLA subtypes. It can be used to treat various cancers caused by KRAS G12D positivity.

The present invention belongs to the technical field of biology. More specifically, the present invention provides a composition for tumor treatment. The composition comprises an NAMPT inhibitor and a KRAS inhibitor. The present invention also provides use of the NAMPT inhibitor and the KRAS inhibitor in the preparation of an anti-tumor drug. Preferably, the tumor is non-small cell lung cancer.

The application discloses biomarkers, kits and application thereof for breast cancer detection. Specifically disclosed are application of biomarkers and / or substances for detecting the biomarkers in breast cancer gene detection, wherein the biomarkers include 13 gene mutation sites, namely AKT1, EGFR, ERBB2, ERBB3, ESR1, FBXW7, KRAS, MTOR, PDGFRA, PIK3CA, PTEN, SF3B1 and TP53. The application also discloses a breast cancer gene mutation detection method, which covers 173 mutation sites of 13 genes, reduces the number of detection reactions by designing a primer panel, realizes simultaneous coverage of more gene mutation sites by using fewer primers, and completes library construction through one round of PCR amplification, is short in operation time, and is high in sensitivity and can reach 0.2%.

The invention discloses a KRAS mutant non-small cell lung cancer marker identification method and system based on deep learning. The method comprises the following steps: collecting transcriptome and proteome multi-omics data of KRAS mutant and wild non-small cell lung cancer patients, and performing missing value processing and standardization to complete data preprocessing; constructing a multi-channel variational auto-encoder (VAE) model, designing an independent encoder channel for transcriptome and proteome data, and training the model by adopting a dynamic training strategy and a staged KLD preheating strategy to extract potential features; after the potential features are fused, a PLS-DA model is constructed, and log2FCgt is combined; 1, adj. Plt; 0.05, VIPgt; 1.5 and KL divergence gt; and the KRAS mutant non-small cell lung cancer specific marker is identified by a multiple screening mechanism of 0.8. According to the method, deep fusion and accurate analysis of multi-omics data are realized, the accuracy and specificity of marker recognition are improved, and efficient technical support is provided for diagnosis, treatment target discovery and individualized treatment of the KRAS mutant non-small cell lung cancer.

Provided herein is a method of treating a cancer comprising a KRAS G12C mutation in a patient, the method comprising administering to the patient sotorasib and an anti-epidermal growth factor receptor (EGFR) antibody in an amount effective to treat the cancer. Further provided is a method further comprising administering to the patient FOLFIRI (irinotecan, 5-FU and leucovorin).

The present invention relates to a compound that may be useful for inhibiting RAS protein. More specifically, the present invention relates to a compound for inhibiting broad-spectrum KRAS mutant protein. Therefore, the compound of the present invention can be used to treat conditions mediated by KRAS protein. For example, the compound can be used to treat cancer.

This disclosure relates to compounds which are degraders of son of sevenless homolog 1 (SOS1) and their use in treating cancers, in particular KRAS-mutant cancers.

This invention relates to a pharmaceutical composition for the prevention or treatment of cancer containing siRNA as an active ingredient, which has been shown to exhibit excellent anticancer effects by significantly suppressing the cell proliferation effect of colorectal cancer or pancreatic cancer, and by reducing the expression level of KRAS mRNA. Furthermore, it can be usefully utilized as an excellent anticancer agent because it reduces tumor size and weight while maintaining the individual's body weight.

The present disclosure provides methods and compositions for adoptive T cell therapy, in particular extracellular binding proteins that target KRAS peptides, host cells comprising the binding proteins, and methods of use and production thereof.

Provided are certain bifunctional compounds that cause degradation of K-ras G12D via ubiquitin proteasome pathway and are therefore useful for the treatment of diseases mediated by K-ras G12D. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

The invention belongs to the technical field of biological medicines, and particularly relates to application of an HS2ST1 inhibitor in preparation of a medicine for treating KRAS inhibitor drug-resistant tumors. At present, more than 50% of KRAS inhibitor drug-resistant patients have unclear mechanisms and lack of effective intervention targets, and HS2ST1 is identified as a key regulation target of KRAS inhibitor drug resistance for the first time. Researches find that the expression of HS2ST1 in KRAS inhibitor drug-resistant cells is significantly up-regulated; functional experiments prove that targeted intervention of the HS2ST1 can effectively enhance the curative effect of the KRAS inhibitor and reverse the drug resistance phenotype of the KRAS inhibitor, and a new strategy and a potential treatment direction are provided for overcoming KRAS targeted treatment drug resistance.

Compounds of formula (I) [Formula 1] A pharmaceutical combination comprising: (a) a Raf inhibitor that is TIFF2026503267000030.tif4686 or a pharmaceutically acceptable salt thereof; (b) a KRAS G12C inhibitor T; and / or (c) trametinib.

The present invention relates to: an antibody targeting a mutation of KRAS as an intracellular oncoprotein; or a fusion protein in which a cancer cell-penetrating peptide is linked to a single-chain variable fragment of the antibody by a genetic expression method or a chemical bonding method; and a tumor therapeutic use thereof. The fusion protein thus produced has the benefit of maximizing an anti-tumor or anticancer effect of the antibody or the single-chain variable fragment of the antibody targeting an intracellular oncoprotein or an oncomutant protein by effectively invading tumor cells.