azd-1152 and Lung-Neoplasms

azd-1152 has been researched along with Lung-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for azd-1152 and Lung-Neoplasms

Article	Year
Discovery and Synthesis of a Pyrimidine-Based Aurora Kinase Inhibitor to Reduce Levels of MYC Oncoproteins. Journal of medicinal chemistry, 2021, 06-10, Volume: 64, Issue:11 The A-type Aurora kinase is upregulated in many human cancers, and it stabilizes MYC-family oncoproteins, which have long been considered an undruggable target. Here, we describe the design and synthesis of a series of pyrimidine-based derivatives able to inhibit Aurora A kinase activity and reduce levels of cMYC and MYCN. Through structure-based drug design of a small molecule that induces the DFG-out conformation of Aurora A kinase, lead compound Topics: Animals; Aurora Kinase A; Aurora Kinase B; Binding Sites; Cell Proliferation; Down-Regulation; Drug Design; Drug Evaluation, Preclinical; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred ICR; Molecular Docking Simulation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-myc; Pyrimidines; Small Cell Lung Carcinoma; Structure-Activity Relationship; Xenograft Model Antitumor Assays	2021
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

Article

Year

Discovery and Synthesis of a Pyrimidine-Based Aurora Kinase Inhibitor to Reduce Levels of MYC Oncoproteins.

Journal of medicinal chemistry, 2021, 06-10, Volume: 64, Issue:11

The A-type Aurora kinase is upregulated in many human cancers, and it stabilizes MYC-family oncoproteins, which have long been considered an undruggable target. Here, we describe the design and synthesis of a series of pyrimidine-based derivatives able to inhibit Aurora A kinase activity and reduce levels of cMYC and MYCN. Through structure-based drug design of a small molecule that induces the DFG-out conformation of Aurora A kinase, lead compound

Topics: Animals; Aurora Kinase A; Aurora Kinase B; Binding Sites; Cell Proliferation; Down-Regulation; Drug Design; Drug Evaluation, Preclinical; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred ICR; Molecular Docking Simulation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-myc; Pyrimidines; Small Cell Lung Carcinoma; Structure-Activity Relationship; Xenograft Model Antitumor Assays

2021

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