azd4547 and Carcinoma--Non-Small-Cell-Lung

azd4547 has been researched along with Carcinoma--Non-Small-Cell-Lung* in 1 studies

Other Studies

1 other study(ies) available for azd4547 and Carcinoma--Non-Small-Cell-Lung

Article	Year
Design, Synthesis, and Pharmacological Evaluation of Novel Multisubstituted Pyridin-3-amine Derivatives as Multitargeted Protein Kinase Inhibitors for the Treatment of Non-Small Cell Lung Cancer. Journal of medicinal chemistry, 2017, 07-27, Volume: 60, Issue:14 A novel series of pyridin-3-amine derivatives were designed, synthesized, and evaluated as multitargeted protein kinase inhibitors for the treatment of non-small cell lung cancer (NSCLC). Hit 1 was first disclosed by in silico screening against fibroblast growth factor receptors (FGFR), which was subsequently validated by in vitro experiments. The structure-activity relationship (SAR) of its analogues was then explored to afford novel FGFR inhibitors 2a-2p and 3a-3q. Among them, 3m showed potent inhibition against FGFR1, 2, and 3. Interestingly, compound 3m not only inhibited various phosphorylation and downstream signaling across different oncogenic forms in FGFR-overactivated cancer cells but also showed nanomolar level inhibition against several other NSCLC-related oncogene kinases, including RET, EGFR, EGFR/T790M/L858R, DDR2, and ALK. Finally, in vivo pharmacology evaluations of 3m showed significant antitumor activity (TGI = 66.1%) in NCI-H1581 NSCLC xenografts with a good pharmacokinetic profile. Topics: Aminopyridines; Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Databases, Chemical; Drug Design; Drug Screening Assays, Antitumor; Female; Heterografts; Humans; Indazoles; Lung Neoplasms; Mice; Mice, Nude; Molecular Docking Simulation; Neoplasm Transplantation; Phosphorylation; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyridines; Rats, Sprague-Dawley; Signal Transduction; Stereoisomerism; Structure-Activity Relationship	2017

Article

Year

Design, Synthesis, and Pharmacological Evaluation of Novel Multisubstituted Pyridin-3-amine Derivatives as Multitargeted Protein Kinase Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

Journal of medicinal chemistry, 2017, 07-27, Volume: 60, Issue:14

A novel series of pyridin-3-amine derivatives were designed, synthesized, and evaluated as multitargeted protein kinase inhibitors for the treatment of non-small cell lung cancer (NSCLC). Hit 1 was first disclosed by in silico screening against fibroblast growth factor receptors (FGFR), which was subsequently validated by in vitro experiments. The structure-activity relationship (SAR) of its analogues was then explored to afford novel FGFR inhibitors 2a-2p and 3a-3q. Among them, 3m showed potent inhibition against FGFR1, 2, and 3. Interestingly, compound 3m not only inhibited various phosphorylation and downstream signaling across different oncogenic forms in FGFR-overactivated cancer cells but also showed nanomolar level inhibition against several other NSCLC-related oncogene kinases, including RET, EGFR, EGFR/T790M/L858R, DDR2, and ALK. Finally, in vivo pharmacology evaluations of 3m showed significant antitumor activity (TGI = 66.1%) in NCI-H1581 NSCLC xenografts with a good pharmacokinetic profile.

Topics: Aminopyridines; Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Databases, Chemical; Drug Design; Drug Screening Assays, Antitumor; Female; Heterografts; Humans; Indazoles; Lung Neoplasms; Mice; Mice, Nude; Molecular Docking Simulation; Neoplasm Transplantation; Phosphorylation; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyridines; Rats, Sprague-Dawley; Signal Transduction; Stereoisomerism; Structure-Activity Relationship

2017