665 results about "KRAS" patented technology

Provided are a compound having the structure represented by formula (I) and capable of being used as a KRAS inhibitor, a pharmaceutical composition comprising the compound, a method for preparing the compound, and a use of the compound in treatment of cancer.

Provided herein are compounds, such as compounds of Formula (I), Formula (l-A), Formula (l-B), or Formula (l-C), or pharmaceutically acceptable salts of any one thereof, useful for modulating KRAS GD12 and / or other G12 mutants.

Provided herein are KRAS proteolysis targeting chimeras (PROTACs), compositions comprising the KRAS PROTACs, and methods of making and using the KRAS PROTACs, e.g., to promote degradation of KRAS and / or treat KRAS-associated cancers. In an embodiment, the KRAS PROTAC has the following structural formula: or a pharmaceutically acceptable salt thereof, wherein values for the variables (e.g., Ring A, X4, Y, R2, R3, R4, L', Degron) are as described herein.

Provided herein are KRAS proteolysis targeting chimeras (PROTACs), compositions comprising the KRAS PROTACs, and methods of making and using the KRAS PROTACs, e.g., to promote degradation of KRAS and / or treat KRAS-associated cancers. In an embodiment, the KRAS PROTAC has the structural formula (I) or a pharmaceutically acceptable salt thereof, wherein values for the variables are as described herein.

There is provided herein a compound of formula (I) wherein R1, R2, R3, R4, A, X1, Y, L, Z, R5, R6a, R6b, W and R7 are as defined herein, for use in the treatment of colorectal and / or lung cancer.

Provided is combination therapies that involve a construct has a TIGIT-binding moiety and a PVRIG-binding moiety and a KRAS G12C inhibitor for treating cancer with KRAS G12C mutations. In some cases, the construct is a multispecific antibody or a bispecific antibody that recognizes PVRIG and TIGIT.

Provided herein are compounds, such as compounds of Formula (I), Formula (l-A), Formula (l-AA), or Formula (l-BB), or pharmaceutically acceptable salts of any one thereof, useful for modulating KRAS GD12 and / or other G12 mutants.

Provided herein are compounds, such as compounds of Formula (I), Formula (l-A), Formula (l-AA), or Formula (l-BB), or pharmaceutically acceptable salts of any one thereof, useful for modulating KRAS GD12 and / or other G12 mutants. (I)

The present invention covers imidazo pyrimidine compounds of general formula (I), in which R1, R2, R3, R4 and Z are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of neoplastic disorders, respectively cancer or conditions with dysregulated immune responses or other disorders associated with aberrant KRAS signaling, as a sole agent or in combination with other active ingredients.

Provided herein are methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of an immunomodulator inhibitor and a compound of Formula (II).

The present disclosure provides KRAS inhibitors of formula (I). Methods of treating cancers using the compounds are also provided.

Provided herein are methods of treating cancer by administering a combination therapy comprising a KRAS G12D inhibitor and a PD-1 inhibitor or a PD-L1 inhibitor.

The present invention is directed to the compounds of Formula (A) inhibitors of KRAS(G12D). The inhibitors described herein can be useful in the treatment of diseases or disorders associated with KRAS(G12D), such as Lung cancer, Pancreatic cancer, Colorectal cancer et al. In particular, the invention is concerned with compounds and pharmaceutical compositions inhibiting KRAS(G12D), methods of treating diseases or disorders associated with KRAS(G12D), and methods of synthesizing these compounds.

Provided herein are methods of treating cancer by administering a combination therapy comprising a KRAS G12D inhibitor and an EGFR inhibitor.

The invention relates to the field of medicinal chemistry, in particular to a substituted quinolinone compound targeting KRASG12D and application of the substituted quinolinone compound. Pharmacological tests prove that the affinity effect of the synthesized compound on a KRASG12D mutant is superior to that of a lead compound KAL-21404358. The compounds WY1-014 and WY1-062 have ideal inhibition effects on cells of human lung cancer (A549), human melanoma (A375) and human colon cancer (LOVO). The compound WY1-062 has excellent anti-tumor activity, and the activity of the compound WY1-062 is superior to that of cis-platinum.

Provided herein are methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of a RTK-MAPK pathway inhibitor and a compound of Formula (I).

The present invention relates to four specific macrocyclic compounds for use as inhibitors of KRAS mutant for the treatment of cancer. Example (1): 1-[4-(dimethylamino)-4-methyl-pent-2-ynoyl]-N-[(1S)-1-[[(6S,8S,14S)-22-ethyl-25-fluoro-(21M)-21-[2-[(1S)-1-methoxyethyl]-3-pyridyl]-18,18-dimethyl-9,15-dioxo-5,16-dioxa-2,10,22,28-tetrazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),20,23(27),24-tetraen-8-yl]carbamoyl]-2-methyl-propyl]-4-fluoro-N-methyl-piperidine-4-carboxamide.

The invention relates to the field of medicinal chemistry, in particular to thiazolidinedione compounds containing quinoline structures and application of the thiazolidinedione compounds. The compound can influence the interaction between KRAS and downstream protein cRaf, namely indirectly inhibits the function of KRAS, and further inhibits the proliferation of tumor cells, and the compound and the pharmaceutical preparation thereof can be used for treating a series of diseases caused by KRAS dysfunction, mainly KRASG12D related cancers, such as KRASG12D related cancers, KRASG12D related cancers, KRASG12D related cancers, KRASG12D related cancers, KRASG12D related cancers, KRASG12D related cancers, for example, colon cancer, rectal cancer, pancreatic cancer, lung cancer, endometrial cancer, skin cancer and the like.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a hydroxyl-substituted dihydroisoquinolinone compound. The compound has a good KRAS G12V mutant gene inhibition effect, and can be used for treating tumor diseases related to KRAS G12V gene mutation.

The invention relates to the field of antitumor drugs, in particular to a pharmaceutical composition of a KRAS G12C inhibitor and camptothecin and application of the pharmaceutical composition. The camptothecin and the KRAS G12C inhibitor are combined to play a synergistic effect, a DNA damage repair pathway is inhibited, a better inhibition effect is generated on tumor cells containing KRAS G12C mutation, the dosage required for achieving the same anti-tumor effect is greatly reduced, and the medication safety is improved.

The invention relates to the field of antitumor drugs, in particular to a pharmaceutical composition of a KRAS G12C inhibitor and Ly2090314 and application of the pharmaceutical composition. According to the invention, the Ly2090314 and the KRAS G12C inhibitor are combined to play a synergistic effect, a DNA damage repair pathway is inhibited, a better inhibition effect is generated on tumor cells containing KRAS G12C mutation, the dosage required for achieving the same anti-tumor effect is greatly reduced, and the medication safety is improved.

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 Q61H, G12D, G12V, G12C, G12S, G12A, G12R, or G13D mutation or wild-type KRAS, including wild-type amplified KRAS) and treating diseases or disorders such as cancers in subjects in need thereof.

The present invention provides methods of treating a cancer patient with an inhibitor of KRAS and an anti-CCR8 antibody. These methods are useful for treating a number of cancers, including pancreatic, colorectal, and lung cancers.

The invention relates to compounds of Formula I, II II-1, III, or III-1 and pharmaceutically acceptable salts thereof, and methods of making and using the same. The compounds of the invention are effective in inhibiting and / or degrading KRAS protein with a G12D mutation and are suitable for use in methods of treating cancers mediated, in whole or in part, by KRAS G12D mutation.

The invention provides application of an SRC inhibitor combined with a KRAS-G12C inhibitor to preparation of a medicine for treating KRAS-G12C mutant lung cancer and a medicine composition, and relates to the technical field of biological medicine, compared with independent use of the KRAS-G12C inhibitor, the scheme of the SRC inhibitor combined with the KRAS-G12C inhibitor can effectively inhibit proliferation and survival of KRAS-G12C mutant lung cancer cells, and the application of the SRC inhibitor combined with the KRAS-G12C inhibitor to preparation of the medicine for treating the KRAS-G12C mutant lung cancer can be used for preparing the medicine for treating the KRAS-G12C mutant lung cancer. The compound can effectively inhibit the activation of a KRAS-MARK pathway and an SRC-FAK pathway, the combination of the compound and the compound has a synergistic anti-tumor effect, and the compound and the compound can be directly combined for medication, can also be prepared into a combined preparation for treating KRAS mutant lung cancer, and have a good clinical transformation prospect.

The present invention is directed to the compounds of Formula (IV) inhibitors of KRAS(G12D). The inhibitors described herein can be useful in the treatment of diseases or disorders associated with KRAS(G12D), such as Lung cancer, Pancreatic cancer, Colorectal cancer et al. In particular, the invention is concerned with compounds and pharmaceutical compositions inhibiting KRAS(G12D), methods of treating diseases or disorders associated with KRAS(G12D), and methods of synthesizing these compounds.

The present invention relates to a KRASG12D inhibitor and the use thereof. Specifically, provided in the present invention is a compound as shown in formula (I), and the definition of each substituent in the formula is as described in the description. In addition, the present invention further relates to a composition containing the inhibitor and the use thereof. The compound of the present invention has good tumor growth inhibitory activity, and has good safety.

The present invention relates to the use of a FAK inhibitor in preparing a drug to be jointly used with a KRAS G12C inhibitor to treat a tumor.

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.

Provided is an antibody-drug conjugate for use in the treatment of cancer in which one or more KRAS mutants, particularly a KRAS G12V mutant, a KRAS G12D mutant, and a KRAS G12C mutant, are expressed. Also provided are a drug and a drug-linker conjugate for use in the antibody-drug conjugate.　The present inventors have produced an antibody-drug conjugate with which a heterocyclic compound represented by formula (II) and having an activity of inducing the decomposition of KRAS mutant proteins can be delivered to cancer in which EGFRs are expressed, the production being achieved by linking the compound to an anti-EGFR antibody. The present inventors have also discovered a drug-linker conjugate for use in the antibody-drug conjugate or a salt thereof. In cancer in which EGFRs are expressed, the antibody-drug conjugate induces the decomposition of one or more KRAS mutants, particularly a KRAS G12V mutant protein, a KRAS G12D mutant protein, and a KRAS G12C mutant protein, thereby inhibiting the KRAS mutants and exhibiting an anti-tumor effect.