Welcome to the InfoSci Platform
Reference Hub3
Identification of Pharmacophore for Wild and T877A Mutant Androgen Receptor Antagonist: Challenges in Designing 3D-QSAR For Mutant Protein

Identification of Pharmacophore for Wild and T877A Mutant Androgen Receptor Antagonist: Challenges in Designing 3D-QSAR For Mutant Protein

Divakar Selvaraj, Sivaram Hariharan, Ramanathan Muthiah
Copyright: © 2017 |Volume: 2 |Issue: 2 |Pages: 15
ISSN: 2379-7487|EISSN: 2379-7479|EISBN13: 9781522515968|DOI: 10.4018/IJQSPR.2017070105
Cite Article Cite Article

MLA

Selvaraj, Divakar, et al. "Identification of Pharmacophore for Wild and T877A Mutant Androgen Receptor Antagonist: Challenges in Designing 3D-QSAR For Mutant Protein." IJQSPR vol.2, no.2 2017: pp.47-61. http://doi.org/10.4018/IJQSPR.2017070105

APA

Selvaraj, D., Hariharan, S., & Muthiah, R. (2017). Identification of Pharmacophore for Wild and T877A Mutant Androgen Receptor Antagonist: Challenges in Designing 3D-QSAR For Mutant Protein. International Journal of Quantitative Structure-Property Relationships (IJQSPR), 2(2), 47-61. http://doi.org/10.4018/IJQSPR.2017070105

Chicago

Selvaraj, Divakar, Sivaram Hariharan, and Ramanathan Muthiah. "Identification of Pharmacophore for Wild and T877A Mutant Androgen Receptor Antagonist: Challenges in Designing 3D-QSAR For Mutant Protein," International Journal of Quantitative Structure-Property Relationships (IJQSPR) 2, no.2: 47-61. http://doi.org/10.4018/IJQSPR.2017070105

Export Reference

Mendeley
Favorite Full-Issue Download

Abstract

Androgen increases the proliferation of prostate cancer cells by activating the androgen receptor (AR). AR antagonists block the androgen mediated proliferation and are used to treat prostate cancer. Antagonist resistance occurs due to the expression of mutations in AR. One particular mutation, T877A, was frequently expressed in relapsed patients. Presently, there is no antagonist in the market without the problem of resistance developing over the period of treatment. A plausible reason for this shortcoming could be the lack of designing because of the unavailability of AR-crystal structure in antagonist bound conformation. Hence, 3D-QSAR becomes a major tool in identification of novel AR antagonists. Three models, ADDHRR.295, AHHRR.266, and AHRR.63 were designed for wild type, T877A mutant, and full (active at both wild and mutant types) AR antagonists respectively. There is a major difference in the angles and lengths of the pharmacophore site points among the 3D-QSAR models. The generated pharmacophore for full antagonists was then used for screening the SPECS database with filters for identifying hits.

Data Sets

Request Access

You do not own this content. Please login to recommend this title to your institution's librarian or purchase it from the IGI Global bookstore.