Multiclass Comparative Virtual Screening to Identify Novel Hsp90 Inhibitors: A Therapeutic Breast Cancer Drug Target

Title:Multiclass Comparative Virtual Screening to Identify Novel Hsp90 Inhibitors: A Therapeutic Breast Cancer Drug Target

Volume: 15 Issue: 1

Author(s): Nageswara Rao Dunna, Srinivas Bandaru, Uday Raj Akare, Siddheshwar Rajadhyax, Venkata Ravi Gutlapalli, Mukesh Yadav and Anuraj Nayarisseri

Affiliation:

Keywords: Drug-likeness, Hsp90 inhibitors, Molecular docking, Virtual screening.

Abstract: Since the discovery of Hsp90, a decade ago, it has surfaced as a potential target in breast cancer therapy along with other cancers. In present study, we have selected seven established Hsp inhibitors viz., PU3, CCT-018159, CNF-2024, SNX-5422, NVP (AUY-922), EGCG and IPI-504 used in the treatment of cancer. Considering these seven inhibitors as a parent compound, ligand based search was carried out with 90% similarity in Pubchem database (31 million compounds). All the similar molecules belonging to respective parent compound along with similar compound were subjected to virtual screening using MolDock and PLP algorithm aided molecular docking. Compounds with highest docking rerank scores were selected and filtered through Lipinski’s drug-likeness filters and toxicity parameters. New candidate (Pubchem CID: 11363378) qualified to demonstrate considerable affinity towards Hsp90. The selected compound was further pharmcophorically incited for receptor- ligand interactions like H-bond, electrostatic, hydrophobic interactions etc.

Cite this article as:

Dunna Rao Nageswara, Bandaru Srinivas, Akare Raj Uday, Rajadhyax Siddheshwar, Gutlapalli Ravi Venkata, Yadav Mukesh and Nayarisseri Anuraj, Multiclass Comparative Virtual Screening to Identify Novel Hsp90 Inhibitors: A Therapeutic Breast Cancer Drug Target, Current Topics in Medicinal Chemistry 2015; 15 (1) . https://dx.doi.org/10.2174/1568026615666150112113627