39 results about "Activating mutation" patented technology

The present invention relates to the use of Fibroblast Growth Factor Receptor I (FGFR1) extracellular domain (ECD) polypeptides for treatment of cancers characterized by ligand dependent activating mutations in Fibroblast Growth Factor Receptor 2 (FGFR2). For example, the present invention relates to the treatment of endometrial cancers and other cancers wherein tumor cells express FGFR2 mutants in the IgII-IgIII hinge region or IgIII domain of the protein, such as at amino acid positions 252 and/or 253.

The present invention is based, at least in part, on the generation of an animal model of pancreatic adenocarcinoma which recapitulates the genetic and histological features of human pancreatic adenocarcinoma, including the initiation, maintenance, and progression of the disease. Accordingly, the present invention provides animal models of cancer, e.g., pancreatic adenocarcinoma, wherein an activating mutation of Kras has been introduced, and any one or more known or unknown tumor suppressor genes or loci, e.g., Ink4a/Arf, Ink4a, Arf, p53, Smad4/Dpc, Lkb1, Brca2, or Mlh1, have been misexpressed, e.g., have been misexpressed leading to decreased expression or non-expression. The animal models of the invention may be used, for example, to identify biomarkers of pancreatic cancer, to identify agents for the treatment or prevention of pancreatic cancer, and to evaluate the effectiveness of potential therapeutic agents.

Epidermal growth factor receptor (EGFR) inhibitors are provided. In particular, 4-substituted-2-(N-(5-substituted allyl amide)phenyl)amino)pyrimidine derivatives of formula (I), a preparation method and use thereof as an EGFR inhibitor are provided. The 4-substituted-2-(N-(5-substituted allyl amide)phenyl)amino)pyrimidine derivatives of formula (I) have inhibitory activity against the L858R EGFR mutant, the T790M EGFR mutant and the exon 19 deletion activating mutant, and can be used to treat diseases mediated alone or in part by EGFR mutant activity. The derivatives of formula (I) can be used to treat and/or prevent cancers, particularly non-small cell lung cancer.

The present invention disclosed a class of pyrimidine or pyridine compounds, pharmaceutically acceptable salts, stereoisomers, prodrugs and solvates thereof, preparation method therefor and pharmaceutical compositions and pharmaceutical uses thereof. The compounds can inhibit the variants of EGFR (Epidermis Growth Factor Receptor) proteinases, and therefore can inhibit the growth of a variety of tumor cells effectively. The compounds can be used to prepare antitumor drugs, used for the treatment, combined therapy or prevention of various different cancers. The compounds can overcome the drug resistance induced by the existing first-generation EGFR inhibitors such as gefitinib, erlotinib and so on. Particularly, the compounds can be used to prepare drugs for treating or preventing diseases, disturbances, disorders or conditions mediated by epidermis growth factor receptor variants (such as L858R activated mutants, Exon19 deletion activated mutants and T790M resistant mutants).

The present invention related to methods and reagents for generating and using activating mutations of receptors and ion channels.

The present invention relates to the field of melanoma diagnosis and therapy. In particular, the present invention relates to c-kit activating mutations present in melanoma, and their use for melanoma evaluation and diagnosis, melanoma prognosis, melanoma progression monitoring, and prescribing therapeutic strategies such as treatment with imatinib or other kinase inhibitors.

The present invention provides methods of detecting activating mutations in exon 4 of a GNAQ or a GNA11 gene in a melanocytic neoplasm for diagnostic and prognostic purposes. The invention further provides methods of treating such melanocytic neoplasm by modulating the activity of the mutated GNAQ or GNA11.

The present invention relates to a p53-activating agent capable of transferring wild-type tumor protein p53 (p53) from an inactive conformation into an active conformation capable of inducing apoptosis, for use in the treatment of melanoma, wherein said p53-activating agent is administered simultaneously or sequentially with a BRAF-inhibiting agent capable of inhibiting activity of serine/threonine-protein kinase B-Raf (BRAF) comprising an activating mutation.

The present invention relates to certain 2-(2,4,5-substituted-anilino)pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exon19 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.

The present invention relates to certain 2-(2,4,5-substituted-anilino)pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exon19 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.

The invention belongs to the field of medicine synthesis and specifically relates to indole-1-carbonate compound shown in a general formula (I), a pharmaceutically acceptable salt, a deuterium compound or a solvate of the indole-1-carbonate compound, a preparation method thereof and application thereof in preparing medicine for selectively inhibiting active EGFR resistance mutation T790M and activated mutation. The formula (I) is shown in the specification.

An isolated peptide is provided. The peptide comprises an amino acid sequence arranged in a space and configuration that allow interaction of the peptide with the DNA Binding Domain (DBD) of p53 through at least one residue of the DBD by which pCAP 250 (SEQ ID NO: 1) binds the DBD, wherein the peptide at least partially reactivates a mutant p53 protein, with the proviso that the peptide is not SEQ ID NO: 59-382.

A method of treating a cancer in a subject in need thereof is disclosed. The cancer can be an esophageal cancer, a uterine cancer, a liver cancer, or a cholangiocarcinoma. The method comprises administering to the subject an effective amount of an anti-Dkk-1 antibody or antigen binding-fragment thereof, wherein the subject is determined to have a constitutively activating mutation of the beta-catenin protein.

In accordance with the invention, a novel activating mutation (alanine 572 to valine) in JAK3 kinase has been discovered in human acute myelogenous leukemia (AML). The mutant JAK3 kinase was confirmed to drive the proliferation and survival of acute megakaryoblastic leukemia (AML-M7). The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant JAK3 kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the mutant polypeptides. The disclosed identification of this new mutant protein and enables new methods for determining the presence of mutant JAK3 kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the mutant proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

Diagnostic and therapeutic applications for endometrial cancer are described. The diagnostic and therapeutic applications are based on certain activation mutations in the FGFR2 gene and its expression products. The present invention is directed to nucleotide sequences, amino acid sequences, probes, and primers related to FGFR2 activation mutants and kits comprising these mutants to diagnosis and classify endometrial cancer in a subject.

A compound for use in treating a disease associated with activating mutations in RAS, or for use in treating a disease treatable by a reduction in RAS activity, is selected from a compound of Formula(I), salts and esters thereof. The compounds are particularly useful in treating cancer.

The present invention relates to the discovery of a method for identifying a treatment regimen for a patient diagnosed with cancer, predicting patient resistance to therapeutic agents and identifying new therapeutic agents, obtaining the specificity profile of a therapeutic agent, and of a method of designing a scaffold of a therapeutic agent directed against a drug-resistant target. Specifically, the present invention relates to the use of an algorithm to identify a mutation in a kinase, determine if the mutation is an activation or resistance mutation and then to suggest an appropriate therapeutic regimen. The invention also relates to the use of a pattern matching algorithm and a crystal structure library to predict the functionality of a gene mutation, predict the specificity of small molecule kinase inhibitors and for the identification of new therapeutic agents.