36 results about "Mutant RAS" patented technology

Provided herein are compositions, reactions mixtures, mutant Ras proteins, kits, substrates, and systems for selecting a Ras antagonist, as well as methods of using the same.

Inhibitors of Ras protein, methods to modulate the activity of Ras protein, and methods of treatment of disorders mediated by Ras protein are provided. A method for regulating activity of a K-Ras, H-Ras or N-Ras mutant protein with a compound is described. Disorders that can be treated include cancer, such as hematological cancer, pancreatic cancer, MYH associated polyposis, colorectal cancer, or lung cancer.

Provided herein are compositions, reactions mixtures, mutant Ras proteins, kits, substrates, and systems for selecting a Ras antagonist, as well as methods of using the same.

The invention provides a G12C mutant K-Ras protein irreversible inhibitor, the invention also discloses the G12C mutant K-Ras protein irreversible inhibitor and a preparation method and use thereof.

The invention discloses a nitric oxide (NO) donor-type farnesyl thiosalicylic acid (FTA) derivative, and pharmaceutically acceptable salt, a preparation method and medical application thereof. The FTA derivative is a compound obtained by carrying out heterozygosis on a NO donor furazan nitrogen oxide and Ras protein inhibitor FTA by an ester bond or an amido bond. Pharmacological test results show that the FTA derivative can reserve the Ras protein inhibiting activity of FTA and simultaneously releases high-concertration NO to induce cancer cell apoptosis and enhance the inhibiting action on cancer cell proliferation; compared with the FTA, the FTA derivative has more excellent anti-tumor activity, and therefore, the compound can be suitable for treating various clinical malignant tumours.

The invention discloses a monoclonal antibody hybrid tumor cell strain KGH-R1 of broad spectrum anti-human p21Ras protein and a monoclonal antibody, belongs to the field of medical biology, and in particular relates to the monoclonal antibody hybrid tumor cell strain KGH-R1 of broad spectrum anti-human p21Ras protein and the monoclonal antibody. The hybrid tumor is preserved in a China center for type culture collection in September 23rd 2011, and has the preservation number of CCTCCNO: C201197. A mouse monoclonal antibody which has synchronous antagonism to three types of active Ras protein is finally obtained; and the monoclonal antibody which aims at a p21Ras protein target can be used for protein clinical test, can also construct an intracellular antibody, has an active tumor prevention function by inhibiting tissue vicious transformation through resisting overexpressed Ras protein, and has an active target antitumous effect on the tumor which corresponds to the overexpressed Ras protein.

Mutant ras oncogene peptides may induce specific anti-ras cellular immune responses in vaccinated patients. Moreover, a human CD8+ CTL epitope(s) reflecting a specific point mutation in the K-ras oncogene at codon 12 was identified. The mutant ras peptide has implications for both active and passive immunotherapies in selected carcinoma patients. A nested 10-mer peptide was identified [i.e., ras5-14(Asp12)], which was shown to bind to HLA-A2 and display specific functional capacity for expansion of the in vivo-primed CD8+ CTL precursors.

The present disclosure provides inhibitors of Ras protein of Formula (I-A):Also disclosed are methods to modulate the activity of Ras protein and methods of treatment of disorders mediated by Ras protein with compounds of Formula (I-A).

Described herein is a method of modulating sumoylation of a Ras protein by small ubiquitin-like modifier (SUMO) proteins. Provided herein is a method for regulating the activity of a Ras protein. Also provided is a treatment of proliferative diseases, such as cancer, by introducing specific mutations to a mutant Ras protein that is associated with the proliferative disease. Described herein is a modified Ras protein. Described herein are recombinant vectors, cells comprising the vectors expressing the modified Ras proteins. Provided herein is an antibody that specifically binds to a sumoylated Ras protein. Described herein is a method for identifying an agent that interferes with the sumoylation of a Ras protein. Also described herein are therapeutic and prophylactic compositions. Also provided herein is a method of using a modified Ras protein to replace an endogenous mutant Ras protein that is associated with a proliferative disease.

A tumor-specific cytosol-internalized RAS-inhibiting antibody, in which modified variable heavy chain region and variable light chain region are combined, according to the present invention facilitates development into a therapeutic drug due to a high production yield, and can effectively suppress mutant RAS by means of tumor-specific internalization into the cytosol, and thus effective anti-cancer activity can be expected as a stand-alone drug or in parallel treatment with existing medicine.

There is disclosed a peptide suitable for eliciting an immune response. The peptide corresponds to a fragment of the RAS protein, and comprises a region of 8 amino acids which includes a mutated position of the RAS protein. Said region has at least 6 amino acid residues, other than the mutated position, which are identical to the corresponding region of the RAS protein. The peptide has a point mutation at the amino acid corresponding to the mutated position, and the mutated position is position 146 or 117 of the RAS protein.

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.

A Ras protein degradation inducing molecule that can induce degradation of Ras proteins, and a pharmaceutical composition that contains this Ras protein degradation inducing molecule are provided. The Ras protein degradation inducing molecule is a conjugate of a Ras protein affinity molecule which has affinity to Ras proteins, and a proteolysis-inducing tag which has affinity to protease and does not inhibit proteolysis of proteins by the protease.

Pyrazolopyrimidine RAS modulating compounds and methods of using the same are provided. The pyrazolopyrimidine 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.

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.

Pyrazolopyrimidine RAS modulating compounds and methods of using the same are provided. The pyrazolopyrimidine 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 present invention relates to compounds of Formula I as defined herein, and salts and solvates thereof. (I) The present invention also relates to pharmaceutical compositions comprising compounds of Formula (I), and to compounds of Formula (I) for use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which inhibition of a RAS-effector protein-protein interaction is implicated.

Mutant ras oncogene peptides may induce specific anti-ras cellular immune responses in vaccinated patients. Moreover, a human CD8+ CTL epitope(s) reflecting a specific point mutation in the K-ras oncogene at codon 12 was identified. The mutant ras peptide has implications for both active and passive immunotherapies in selected carcinoma patients. A nested 10-mer peptide was identified [i.e., ras5-14(Asp12)], which was shown to bind to HLA-A2 and display specific functional capacity for expansion of the in vivo-primed CD8+ CTL precursors.

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

The present invention relates to novel substituted benzene disulfonamides, as well as pharmaceutical compositions containing at least one of these substituted benzene disulfonamides together with at least one pharmaceutically acceptable carrier, excipient and / or diluent. Said substituted benzene disulfonamides are binding to the prenyl binding pocket of PDE6δ and therefore, are useful for the prophylaxis and treatment of cancer by inhibition of the binding of PDE6δ to farnesylated Ras proteins and thereby, inhibition of oncogenic Ras signaling in cells.

The invention relates to an application of a pharmaceutical composition in inhibition of ras proto-oncogene overexpression, and specifically, relates to the application in preparation of anti-tumor drugs for inhibiting ras proto-oncogene overexpression. Specifically, the pharmaceutical composition contains radix ginseng, radix ophiopogonis and schisandra chinensis fruits. Researches indicate that about 90% of pancreatic cancer, 50% of colon cancer, 30%-40% of lung adenocarcinoma and 5%-40% of leukemia are caused by the ras proto-oncogene overexpression, and a Ras protein becomes a universally accepted target for screening related malignant tumor drugs. Animal experiments indicate that the pharmaceutical composition can specifically down-regulate overexpression caused after ras proto-oncogene mutation, but does not act on wild-type ras proto-oncogenes, so that the pharmaceutical composition is low in toxicity and has no teratogenic effect and no reproduction toxicity; the pharmaceutical composition can be used for preparation of drugs for tumors caused by overexpression after ras proto-oncogene mutation, can be mixed with any one of pharmaceutically acceptable auxiliary materials to prepare various dosage forms, and is expected to be developed into a new-generation antitumor drugs.

A tumor-specific cytosol-internalized RAS-inhibiting antibody, in which modified heavy-chain variable region and a light-chain variable region are combined, according to the present disclosure facilitates development into a therapeutic drug due to a high production yield, and can effectively suppress mutant RAS by means of tumor-specific internalization into the cytosol, and thus effective anti-cancer activity can be expected as a stand-alone drug or in combination treatment with existing medicine.

A Ras protein degradation inducing molecule that can induce degradation of Ras proteins, and a pharmaceutical composition that contains this Ras protein degradation inducing molecule are provided. The Ras protein degradation inducing molecule is a conjugate of a Ras protein affinity molecule which has affinity to Ras proteins, and a proteolysis-inducing tag which has affinity to protease and does not inhibit proteolysis of proteins by the protease.

RAS modulating compounds and methods of using the same are provided. The subject compounds comprise a core fused bicyclic group based on a quinoline-type scaffold having two fused six-membered aryl or heteroaryl rings, linked to a cyclic group (A) through the 2-position via a linker. The linked cyclic group can be an optionally substituted cyclopentyl or pyrrolidine group. 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 invention discloses a nitric oxide (NO) donor-type farnesyl thiosalicylic acid (FTA) derivative, and pharmaceutically acceptable salt, a preparation method and medical application thereof. The FTA derivative is a compound obtained by carrying out heterozygosis on a NO donor furazan nitrogen oxide and Ras protein inhibitor FTA by an ester bond or an amido bond. Pharmacological test results show that the FTA derivative can reserve the Ras protein inhibiting activity of FTA and simultaneously releases high-concertration NO to induce cancer cell apoptosis and enhance the inhibiting action on cancer cell proliferation; compared with the FTA, the FTA derivative has more excellent anti-tumor activity, and therefore, the compound can be suitable for treating various clinical malignant tumours.

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 invention relates to an application of schisandra chinensis in inhibition of ras proto-oncogene overexpression, and specifically, relates to the application of the schisandra chinensis in preparation of anti-tumor drugs for inhibiting ras proto-oncogene overexpression. Researches indicate that about 90% of pancreatic cancer, 50% of colon cancer, 30%-40% of lung adenocarcinoma and 5%-40% of leukemia are caused by the ras proto-oncogene overexpression, and a Ras protein becomes a universally accepted target for screening drugs resistant to related malignant tumors. Animal experiments indicate that schisandra chinensis can specifically down-regulate overexpression caused after ras proto-oncogene mutation, but does not act on wild-type ras proto-oncogenes, so that the toxicity is low. The invention provides the new use of schisandra chinensis, and schisandra chinensis can be applied in preparation of the anti-tumor (tumors caused by the ras proto-oncogene overexpression) drugs.

The invention provides a peptide or peptidomimetic that is derived from or based upon the amino acid sequence of the C-terminal α-helix or hypervariable region (HVR) or a Ras protein, a nucleic acid encoding the peptide or peptidomimetic, and methods employing the same.