Molecular docking and 3D QSAR studies of substituted 4-amino-1H-pyrazolo[3,4-d]pyrimidines as insulin-like growth factor-1 receptor (IGF1R) inhibitors

Insulin-like growth factor-1 receptor (IGF1R) is one of receptor tyrosine kinase that plays a significant role in cancer and has been pursued as drug target for cancer therapy. Molecular docking and comparative molecular field analysis (CoMFA) studies were carried out on the series of substituted 4-amino-1H-pyrazolo3,4-d]pyrimidines IGF1R inhibitors. The conformations of these inhibitors from docking results provided a reliable conformational alignment scheme for 3D QSAR model. Based on these conformations, significant CoMFA model was performed with a leave-one-out cross-validated q ² of 0.590. The noncross-validated analysis revealed r ² value of 0.941, F?=?34.882, and an estimated standard error of 0.178 with four optimum components. The predictive ability of our model was validated by the testing set with a conventional r ² value of 0.925. The effective model may be used to design more potent IGF1R inhibitors and predict their activities before synthesis or experimental test.