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Virtual screening of novel compounds as potential ERα inhibitors



J. TilakVijay*, K. Vivek Babu, A. Uma



Centre for Biotechnology, Institute of Science &Technology, Jawaharlal Nehru Technological University, Hyderabad, Telungana, India



J. TilakVijay E-mail:


Article Type

Research Article



Received April 2, 2019; Accepted April 12, 2019; Published April 30, 2019



Majority of breast cancers diagnosed today are estrogen receptor (ER)-positive, however, progesterone receptor-positive (PR-positive) is also responsible for breast cancer. Tumors that are ER/PR-positive are much more likely to respond to hormone therapy than tumors that are ER/PR-negative. Nearly 105 ERα inhibitors from literature when docked resulted in 31 compounds (pyrazolo[1,5-a]pyrimidine analogs and chromen-2-one derivatives) with better binding affinities. The maximum score obtained was -175.282 kcal/mol for compound, [2-(4-Fluoro-phenylamino)-pyridin-3-yl]-{4-[2-phenyl-7- (3, 4, 5-trimethoxy-phenyl)-pyrazolo[1,5-a]pyrimidine-5-carbonyl]-piperazin-1-yl}-methanone. The major H-bond interactions are observed with Thr347. In pursuit to identify novel ERα inhibitory ligands, virtual screening was carried out by docking pyrazole, bipyrazole, thiazole, thiadiazole etc scaffold analogs from literature.34 bipyrazoles from literature revealed Compound 2, ethyl 5-amino-1-(5-amino-3-anilino-4-ethoxycarbonyl-pyrazol-1-yl)-3-anilino-pyrazole-4-carboxylate, with -175.9 kcal/mol binding affinity with the receptor, where a favourable H-bond was formed with Thr347.On the other hand, screening 2035 FDA approved drugs from Drug Bank database resulted in 11 drugs which showed better binding affinities than ERα bound tamoxifen. Consensus scoring using 5 scoring schemes such as Mol Dock score, mcule, SwissDock, Pose&Rank and DSX respectively resulted in better rank-sumsfor Lomitapide, Itraconazole, Cobicistat, Azilsartanmedoxomil, and Zafirlukast.



molecular docking, virtual screening, ERα, estrogen, bipyrazoles, drug Bank



Tilak Vijay et al. Bioinformation 15(5): 321-332 (2019)


Edited by

P Kangueane






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.