brivanib and Lung-Neoplasms

brivanib has been researched along with Lung-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for brivanib and Lung-Neoplasms

Article	Year
The target landscape of clinical kinase drugs. Science (New York, N.Y.), 2017, 12-01, Volume: 358, Issue:6367 Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cytokines; Drug Discovery; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Myeloid, Acute; Lung Neoplasms; Mice; Molecular Targeted Therapy; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Proteomics; Xenograft Model Antitumor Assays	2017
Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth fa Journal of medicinal chemistry, 2008, Mar-27, Volume: 51, Issue:6 A series of amino acid ester prodrugs of the dual VEGFR-2/FGFR-1 kinase inhibitor 1 (BMS-540215) was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound. These prodrugs were evaluated for their ability to liberate parent drug 1 in in vitro and in vivo systems. The l-alanine prodrug 8 (also known as brivanib alaninate/BMS-582664) was selected as a development candidate and is presently in phase II clinical trials. Topics: Administration, Oral; Alanine; Animals; Biological Availability; Carcinoma; Cell Proliferation; Clinical Trials, Phase II as Topic; Drug Design; Drug Evaluation, Preclinical; Humans; Intestines; Liver; Lung Neoplasms; Mice; Microsomes; Molecular Structure; Prodrugs; Protein Kinase Inhibitors; Pyrroles; Receptor, Fibroblast Growth Factor, Type 1; Solubility; Stereoisomerism; Triazines; Vascular Endothelial Growth Factor Receptor-2; Water; Xenograft Model Antitumor Assays	2008

Article

Year

The target landscape of clinical kinase drugs.

Science (New York, N.Y.), 2017, 12-01, Volume: 358, Issue:6367

Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cytokines; Drug Discovery; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Myeloid, Acute; Lung Neoplasms; Mice; Molecular Targeted Therapy; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Proteomics; Xenograft Model Antitumor Assays

2017

Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth fa

Journal of medicinal chemistry, 2008, Mar-27, Volume: 51, Issue:6

A series of amino acid ester prodrugs of the dual VEGFR-2/FGFR-1 kinase inhibitor 1 (BMS-540215) was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound. These prodrugs were evaluated for their ability to liberate parent drug 1 in in vitro and in vivo systems. The l-alanine prodrug 8 (also known as brivanib alaninate/BMS-582664) was selected as a development candidate and is presently in phase II clinical trials.

Topics: Administration, Oral; Alanine; Animals; Biological Availability; Carcinoma; Cell Proliferation; Clinical Trials, Phase II as Topic; Drug Design; Drug Evaluation, Preclinical; Humans; Intestines; Liver; Lung Neoplasms; Mice; Microsomes; Molecular Structure; Prodrugs; Protein Kinase Inhibitors; Pyrroles; Receptor, Fibroblast Growth Factor, Type 1; Solubility; Stereoisomerism; Triazines; Vascular Endothelial Growth Factor Receptor-2; Water; Xenograft Model Antitumor Assays

2008