Molecules, Vol. 28, Pages 2490: Virtual Screening for Identification of Dual Inhibitors against CDK4/6 and Aromatase Enzyme

Molecules, Vol. 28, Pages 2490: Virtual Screening for Identification of Dual Inhibitors against CDK4/6 and Aromatase Enzyme Molecules doi: 10.3390/molecules28062490 Authors: Tenzin Adon Dhivya Shanmugarajan Hissana Ather Shaik Mohammad Asif Ansari Umme Hani SubbaRao V. Madhunapantula Yogish Kumar Honnavalli CDK4/6 and aromatase are prominent targets for breast cancer drug discovery and are involved in abnormal cell proliferation and growth. Although aromatase inhibitors have proven to be effective (for example exemestane, anastrozole, letrozole), resistance to treatment eventually occurs through the activation of alternative signaling pathways, thus evading the antiproliferative effects of aromatase inhibitors. One of the evasion pathways is Cylin D-CDK4/6-Rb signaling that promotes tumor proliferation and resistance to aromatase inhibitors. There is significant evidence that the sequential inhibition of both proteins provides therapeutic benefits over the inhibition of one target. The basis of this study objective is the identification of molecules that are likely to inhibit both CDK4/6 and aromatase by computational chemistry techniques, which need further biochemical studies to confirm. Initially, a structure-based pharmacophore model was constructed for each target to screen the sc-PDB database. Consequently, pharmacophore screening and molecular docking were performed to evaluate the potential lead candidates that effectively mapped both of the target...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research