caa a22 4500 467938520 CHVBK 20180406153005.0 cr unu---uuuuu 170328e20060101xx s 000 0 eng 10.1007/s10822-006-9036-4 doi (NATIONALLICENCE)springer-10.1007/s10822-006-9036-4 New leads for selective GSK-3 inhibition: pharmacophore mappingand virtual screening studies [Elektronische Daten] [Dhilon Patel, Prasad Bharatam] Summary: Glycogen Synthase Kinase-3 is a regulatory serine/threonine kinase, which is being targeted for the treatment of a number of human diseases including type-2 diabetes mellitus, neurodegenerative diseases, cancer and chronic inflammation. Selective GSK-3 inhibition is an important requirement owing to the possibility of side effects arising from other kinases. A pharmacophore mapping strategy is employed in this work to identify new leads for selective GSK-3 inhibition. Ligands known to show selective GSK-3 inhibition were employed in generating a pharmacophore map using distance comparison method (DISCO). The derived pharmacophore map was validated using (i) important interactions involved in selective GSK-3 inhibitions, and (ii) an in-house database containing different classes of GSK-3 selective, non-selective and inactive molecules. New Lead identification was carried out by performing virtual screening using validated pharmacophoric query and three chemical databases namely NCI, Maybridge and Leadquest. Further data reduction was carried out by employing virtual filters based on (i) Lipinski's rule of 5 (ii) van der Waals bumps and (iii) restricting the number of rotatable bonds to seven. Final screening was carried out using FlexX based molecular docking study. Springer Science+Business Media, Inc., 2006 diabetes mellitus nationallicence Glycogen Synthase Kinase-3 (GSK-3) nationallicence molecular docking nationallicence pharmacophore mapping nationallicence virtual screening nationallicence Patel Dhilon Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, 160 062, Mohali, Punjab, India aut Bharatam Prasad Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, 160 062, Mohali, Punjab, India aut Journal of Computer-Aided Molecular Design Springer Netherlands 20/1(2006-01-01), 55-66 0920-654X 20:1<55 2006 20 10822 https://doi.org/10.1007/s10822-006-9036-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9036-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Patel Dhilon Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, 160 062, Mohali, Punjab, India aut NATIONALLICENCE 700 1- Bharatam Prasad Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, 160 062, Mohali, Punjab, India aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Springer Netherlands 20/1(2006-01-01), 55-66 0920-654X 20:1<55 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer