38 results about "Mutant RAS" patented technology

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Disclosed are RAS(ON) multi-selective inhibitor compositions and methods of treating RAS protein-related diseases or disorders using an intermittent dosing regimen. RAS(ON) multi-selective inhibitors having tight binding to cyclophilin A (CypA) result in high exposure levels, prolonged tissue retention, and / or slow clearance rates, thereby increasing the risk of inhibition of wild-type RAS in normal tissues. Accordingly, provided herein are methods for the safe and effective dosing of low KD1 RAS(ON) multi-selective inhibitors using an intermittent dosing regimen. Also provided are methods of selecting or identifying such RAS(ON) multi-selective inhibitors suitable for intermittent administration.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The present disclosure generally relates to quick release pharmaceutical dose unit tablets containing small molecule API drugs. In some examples, the API is an inhibitor of Ras proteins, such as K-Ras, H-Ras, and N-Ras, with a G12C mutation. The tablet also contains a disintegrating agent and an excipient. More specifically, the present disclosure relates to pharmaceutical dosage unit tablets containing divariclisib or a pharmaceutically acceptable salt thereof, an ex-particulate disintegrant, and an ex-particulate excipient, as well as a method for preparing the tablets from particles formed by dry granulation.

The present application relates to compounds of formula (A) that inhibit the growth of cancers that express G12D mutant Ras proteins. The molecules of the specification are thus indicated for use in the treatment of cancer that express G12D mutant Ras protein.

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.

The present invention is based on the discovery of extracellular accessible Ras proteins on cancer cells. The present invention provides an antigen binding protein (ABP), such as an antibody or chimeric antigen receptor (CAR), where the ABP comprises at least one first antigen binding domain capable of binding to an extracellular Ras antigen. Further provided are isolated nucleic acids and expression constructs for expressing the ABP of the invention, as well as recombinant host cells expressing the ABP of the invention. The invention also relates to a pharmaceutical composition, a pharmaceutical combination, a compound for medicine and a compound for diagnosing, preventing and / or treating cancer. Finally, the present invention relates to a combination of the ABP, CAR, isolated nucleic acid, expression construct, recombinant host cell or pharmaceutical composition as defined herein with a chemical compound, such as a cerebron (CRBN) inhibitor or a polar organic solvent, such as DMSO, for a method of diagnosis, prevention and / or treatment of cancer.

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 disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Disclosed are RAS(ON) multi-selective inhibitor compositions and methods of treating RAS protein-related diseases or disorders using an intermittent dosing regimen. RAS(ON) multi-selective inhibitors having tight binding to cyclophilin A (CypA) result in high exposure levels, prolonged tissue retention, and / or slow clearance rates, thereby increasing the risk of inhibition of wild-type RAS in normal tissues. Accordingly, provided herein are methods for the safe and effective dosing of low KD1 RAS(ON) multi-selective inhibitors using an intermittent dosing regimen. Also provided are methods of selecting or identifying such RAS(ON) multi-selective inhibitors suitable for intermittent administration.

The present disclosure provides compounds and pharmaceutically acceptable salts thereof, as well as methods for their use. The compounds and methods have a wide range of applications as therapeutic, diagnostic, and research tools. In particular, the subject compositions and methods are useful for reducing the signaling output of oncogenic proteins. In certain embodiments, the present disclosure provides modified Ras proteins comprising a compound covalently bound to one or more amino acid residues of the Ras protein, wherein the modified Ras protein comprises a compound of formula (I').

The present disclosure features methods of treating RAS disorders using Compound (A) or a pharmaceutically acceptable salt thereof. The disclosure also features methods of treating RAS disorders (e.g., cancer) comprising a combination of Compound (A) or a pharmaceutically acceptable salt thereof with an additional therapeutic agent. Compound (A) is a compound having a structure (A):

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The present disclosure features macrocyclic compounds capable of inhibiting Ras proteins and pharmaceutical compositions and protein complexes thereof, as well as their use in the treatment of cancer.

Provided are a macrocyclic compound and an antibody-drug conjugate thereof, specifically, the macrocyclic compound is a targeted RAS protein inhibitor. The invention also provides a preparation method of the macrocyclic compound and the antibody-drug conjugate thereof, and application of the macrocyclic compound and the antibody-drug conjugate thereof in medicine.

The present application encompasses compounds of formula (I) wherein R 1a , R 1b , R 2a , R 2b , Z, R 3 to R 5 , A, p, U, V, W, L and E have the meanings given in the claims and the description, the use of said compounds as inhibitors of mutant Ras family proteins, pharmaceutical compositions and formulations containing such compounds, and the use of said pharmaceutical compositions and formulations as medicaments / medical, especially as medicaments for the treatment and / or prevention of oncogenic diseases.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Provided herein are RAS protein degraders, e.g., a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a RAS-mediated disorder, disease, or condition.RHet-L2-X-L1-R1  (1)

The present disclosure provides macrocyclic compounds and pharmaceutical compositions and protein complexes thereof capable of inhibiting Ras proteins, and their use in treating cancer.

RAS modulating compounds and methods of using the same are provided. The compounds find use in modulating the activity of a target RAS in a sample. The target RAS can be a mutant RAS that is implicated in a disease of interest. In some cases, the subject compounds can inhibit the growth of cancer cells whose progression is driven by kRAS or a mutated kRAS. Methods of treating a subject for a RAS driven disease including administering a therapeutically effective amount of the subject compound are provided. Also provided are pharmaceutical compositions and kits which include the subject compounds.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The present disclosure features macrocyclic compounds capable of inhibiting the Ras protein, as well as pharmaceutical compositions and protein complexes thereof, as well as their use in the treatment of cancer.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The present invention relates to compounds useful for inhibiting RAS proteins. More specifically, the present invention relates to compounds that inhibit a broad spectrum of KRAS muteins, including KRAS G12D. Thus, the compounds of the invention are useful in the treatment of conditions mediated by the KRAS protein. For example, the compounds are useful in the treatment of cancer.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

This invention relates to compositions and methods of treating cancer associated with mutant RAS. In certain aspects, the invention relates to antigenic RAS peptide fragments and T-cell receptors that bind to specific mutant RAS peptide fragments in the context of specific HLA types.

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.