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43 results about "Activating mutation" patented technology

A definition of the term "activating mutation," which refers to a substitution of one amino acid residue by another that confers a new or higher activity upon the protein, is presented.

Method for treating cancer harboring EGFR mutations

ActiveUS20090318480A1Advantageously effective in treatmentReduced responseBiocideOrganic active ingredientsAcquired resistanceActivating mutation
The present invention relates to a method of treatment of patients suffering from cancer and harbouring mutations of EGFR in the tumour, for instance an activating mutation of the EGFR or a mutation responsible for resistance or the emergence of acquired resistance to treatment with reversible EGFR and / or HER2 inhibitors or irreversible inhibitors such as CI-1033, EKB-569, HKI-272 or HKI-357, comprising administering an effective amount of the irreversible EGFR inhibitor BIBW2992 (1) 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline, to a person in need of such treatment, optionally in combination with the administration of a further chemotherapeutic agent, in combination with radiotherapy, radio-immunotherapy and / or tumour resection by surgery, and to the use of a BIBW 2992 (1) for preparing a pharmaceutical composition for the treatment of patients suffering from cancer and harbouring mutations of EGFR in the tumour.
Owner:BOEHRINGER INGELHEIM INT GMBH

Use of fgfr1 extra cellular domain proteins to treat cancers characterized by ligand-dependent activating mutations in fgfr2

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.
Owner:FIVE PRIME THERAPEUTICS

Animal models of pancreatic adenocarcinoma and uses therefor

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.
Owner:THE TRUSTEES OF THE UNIV OF PENNSYLVANIA +1

EGFR inhibitor, preparation method and use thereof

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.
Owner:SHANGHAI HANSOH BIOMEDICAL +1

Diagnostic and treatment methods in subjects having or at risk of developing resistance to cancer therapy

The invention relates to methods of treatment and diagnosis of subjects with cancer. In some aspects, the invention relates to methods of treatment and diagnosis of subjects with cancer, wherein the cancer is characterized by a Notch pathway activation mutation or by resistance to a Notch pathway inhibitor.
Owner:THE BRIGHAM & WOMEN S HOSPITAL INC +3

Pyrimidine or pyridine compounds, preparation method therefor and pharmaceutical uses thereof

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).
Owner:INVENTISBIO CO LTD

Method of diagnosing, classifying and treating endometrial cancer and precancer

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.
Owner:WASHINGTON UNIV IN SAINT LOUIS +1

FUSION GENE OF Kif5b GENE AND Ret GENE, AND METHOD FOR DETERMINING EFFECTIVENESS OF CANCER TREATMENT TARGETING FUSION GENE

In order to identify a gene that can serve as an indicator for predicting the effectiveness of a drug treatment of cancer and to provide a novel method for predicting the effectiveness of a drug treatment targeting said gene, lung adenocarcinomas were subjected to whole-transcriptome sequencing. As a result, in-frame fusion transcripts between the KIF5B gene and the RET gene were identified. The KIF5B-RET gene fusions were detected in 6 out of 319 (2%) LADC specimens from Japanese individuals and 1 out of 80 (1%) LADC specimens from U.S.A. individuals. None of the seven subjects revealed known activating mutations such as EGFR, KRAS or ALK oncogenes; thus, said gene fusions were found to be responsible mutations (driver mutations) for oncogenesis. Since said gene fusions are considered to induce constitutive activation of RET tyrosine kinase protein, it was found that treatments with RET tyrosine kinase inhibitors are effective in patients with detection of said gene fusions.
Owner:NAT CANCER CENT

Method for treating cancer harboring EGFR mutations

The present invention relates to a method of treatment of patients suffering from cancer and harbouring mutations of EGFR in the tumour, for instance an activating mutation of the EGFR or a mutation responsible for resistance or the emergence of acquired resistance to treatment with reversible EGFR and / or HER2 inhibitors or irreversible inhibitors such as CI-1033, EKB-569, HKI-272 or HKI-357, comprising administering an effect ive amount of the irreversible EGFR inhibitor BIBW2992 (1) 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline, to a person in need of such treatment, optionally in combination with the administration of a further chemotherapeutic agent, in combination with radiotherapy, radio-immunotherapy and / or tumour resection by surgery, and to the use of a BIBW 2992 (1) for preparing a pharmaceutical composition for the treatment of patients suffering from cancer and harbouring mutations of EGFR in the tumour.
Owner:BOEHRINGER INGELHEIM INT GMBH

1-Azabicyclo[2.2.2]octan-3-one derivatives and maleimide derivatives and their use for treating cancer tumors

The present invention provides novel compounds, corresponding to formulae I and II, respectively, which are able to reactivate the apoptosis-inducing function of mutant p53 proteins. This reactivation is provided by restoration of sequence-specific DNA-binding activity and transcriptional transactivation function to mutant p53 proteins, and modulation of the conformation-dependent epitopes of the p53 protein. Accordingly, the substances according to the invention will be used in pharmaceutical compositions and methods for treatment of patients suffering from various types of tumors.
Owner:APREA THERAPEUTICS AB

Human melanoma mutation

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.
Owner:UNIV OF UTAH RES FOUND

Gna11 and gnaq exon 4 mutations in melanoma

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.
Owner:THE UNIV OF BRITISH COLUMBIA +1

New strategies for treating melanoma

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.
Owner:UNIV LIBRE DE BRUXELIES +1

Use of FGFR1 extra cellular domain proteins to treat cancers characterized by ligand-dependent activating mutations in FGFR2

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.
Owner:FIVE PRIME THERAPEUTICS

Use of fgfr1 extra cellular domain proteins to treat cancers characterized by ligand-dependent activating mutations in fgfr2

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.
Owner:FIVE PRIME THERAPEUTICS

2 - (2, 4, 5 - substituted -anilino) pyrimidine derivatives as egfr modulators useful for treating cancer

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.
Owner:ASTRAZENECA AB

Method for treating cancer harboring EGFR mutations

The present invention relates to a method of treatment of patients suffering from cancer and harboring mutations of EGFR in the tumor, for instance an activating mutation of the EGFR or a mutation responsible for resistance or the emergence of acquired resistance to treatment with reversible EGFR and / or HER2 inhibitors or irreversible inhibitors such as CI-1033, EKB-569, HKI-272 or HKI-357, comprising administering an effective amount of the irreversible EGFR inhibitor BIBW2992 (1) 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline, to a person in need of such treatment, optionally in combination with the administration of a further chemotherapeutic agent, in combination with radiotherapy, radio-immunotherapy and / or tumor resection by surgery, and to the use of a BIBW 2992 (1) for preparing a pharmaceutical composition for the treatment of patients suffering from cancer and harboring mutations of EGFR in the tumor.
Owner:BOEHRINGER INGELHEIM INT GMBH

2 -(2,4,5-substituted -anilino) Pyrimidine Derivatives As Egfr Modulators Useful For Treating Cancer

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.
Owner:ASTRAZENECA AB

Indole-1-carbonate compound and preparation method and application 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.
Owner:SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI

EGFR inhibitor, preparation method and use thereof

Epidermal growth factor receptor (EGFR) inhibitors are provided. In particular, 4-substituted-2-(N-(5-substituted ally 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 ally 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.
Owner:SHANGHAI HANSOH BIOMEDICAL +1

Peptides and use of same in the treatment of diseases, disorders or conditions associated with a mutant p53

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.
Owner:YEDA RES & DEV CO LTD

Diagnostic and therapeutic methods for cancer

The present invention provides diagnostic and therapeutic methods and compositions for cancer. The invention provides methods of determining whether an individual having a cancer is likely to respondto treatment comprising a pan-RAF dimer inhibitor and a MEK or PI3K inhibitor, methods of predicting responsiveness of an individual having a cancer to treatment comprising a pan-RAF dimer inhibitor and a MEK or PI3K inhibitor, methods of selecting a therapy for an individual having a cancer, and methods of treating an individual having cancer based on the presence of a biomarker of the invention(e.g., a KRAS activating mutation, e.g., a KRAS-G13D mutation, or an NRAS activating mutation).
Owner:F HOFFMANN LA ROCHE & CO AG

Exposing method for transformation-mode nanomaterial induced mammalian cell malignant transformation

The invention discloses an exposing method for transformation-mode nanomaterial induced mammalian cell malignant transformation; normal mouse embryo fibroblasts and mouse embryo fibroblasts with activating mutation are cultured respectively in a culture medium, at least three vessels of cells are collected and divided into at least three groups, each group includes one vessel of normal mouse embryo fibroblasts and one vessel of mouse embryo fibroblasts with activating mutation, and the groups are marked; after the cells grow to logarithmic phase, supernate is removed, DMEM (Dulbecco's modified eagle medium) with fetal calf serum is added to the first group, DMEM with fresh liquid and fetal calf serum is added to the second group, and DMEM with 'transformation-mode' nanomaterial suspension and fetal calf serum is added to the third group; after conditioned media are removed, each vessel of cells in each group is rinsed; cyclic culture is carried out. The method has the advantages of good simplicity, low operation difficulty, low cost, good results reliability and the like, and is suitable for large-scale popularization.
Owner:ANHUI MEDICAL UNIV

Mutant jak3 kinase in human leukemia

InactiveUS20090285796A1Elevated tyrosine kinase activityDrive proliferationOrganic active ingredientsTransferasesHuman leukemiaMutated 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.
Owner:OREGON HEALTH & SCI UNIV

Methods of diagnosing, classifying and treating endometrial cancer and precancer

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.
Owner:TRANSLATIONAL GENOMICS RESEARCH INSTITUTE

Inhibitors of ras oncoprotein, methods of making and methods of use thereof

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.
Owner:UNIV OF LOUISVILLE RES FOUND INC
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