3D-QSAR CoMFA analysis of C5 substituted pyrrolotriazines as HER2 (ErbB2) inhibitors.
Human cancers are characterized by an up-regulation of some of the RTKs (EGFR and HER2) and have been clinically validated as targets for cancer therapy. C4 and C5 substituted pyrrolotriazines showed dual inhibition of HER2 and EGFR protein tyrosine kinases. To explore the relationship between the structures of the aforementioned classes of molecules and their HER2 inhibition, 3D-QSAR CoMFA analysis have been performed. The developed CoMFA model showed statistically significant results with good predictive ability.
Centre for Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160 062 Punjab, India.
Mahendra
M
Awale
C Gopi
CG
Mohan
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D017076:Computer-Aided Design; D015195:Drug Design; D006801:Humans; D021621:Imaging, Three-Dimensional; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results; D014227:Triazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D000970:Antineoplastic Agents; D008024:Ligands; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D018719:Erb-b2 Receptor Tyrosine Kinases; D014227:Triazines; C508053:ERBB2 protein, human