Nagarajan, Shanthi Doddareddy, Munikumar Reddy Choo, Hyunah Cho, Yong Seo Oh, Kwang-Seok Lee, Byung Ho Pae, Ae Nim 2024-01-20T21:33:29Z 2024-01-20T21:33:29Z 2021-09-03 2009-04-01 0968-0896 https://pubs.kist.re.kr/handle/201004/132575 Control of NF-kappa B release through the inhibition of IKK beta has been identified as a potential target for the treatment of inflammatory and autoimmune diseases. We have employed structure based virtual screening scheme to identify lead like molecule from ChemDiv database. Homology models of IKK beta enzyme were developed based on the crystal structures of four kinases. The efficiency of the homology model has been validated at different levels. Docking of known inhibitors library revealed the possible binding mode of inhibitors. Besides, the docking sequence analyses results indicate the responsibility of Glu172 in selectivity. Structure based virtual screening of ChemDiv database has yielded 277 hits. Top scoring 75 compounds were selected and purchased for the IKK beta enzyme inhibition test. From the combined approach of virtual screening followed by biological screening, we have identified six novel compounds that can work against IKK beta, in which 1 compound had highest inhibition rate 82.09% at 10 mu M and IC50 1.76 mu M and 5 compounds had 25.35-48.80% inhibition. (c) 2009 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD KAPPA-B KINASE HIGHLY SELECTIVE INHIBITOR HIT-TO-LEAD POTENT ACTIVATION INFLAMMATION DERIVATIVES BMS-345541 GENERATION STRATEGIES IKK beta inhibitors identification part I: Homology model assisted structure based virtual screening Article 10.1016/j.bmc.2009.02.041 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.17, no.7, pp.2759 - 2766 BIOORGANIC & MEDICINAL CHEMISTRY 17 7 2759 2766 scie scopus 000264637300015 2-s2.0-63149188726 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article KAPPA-B KINASE HIGHLY SELECTIVE INHIBITOR HIT-TO-LEAD POTENT ACTIVATION INFLAMMATION DERIVATIVES BMS-345541 GENERATION STRATEGIES IKK IKK beta Inhibitor kappa B kinase Homology modeling Virtual screening Docking Flex-X Pharmacophore constraints Enrichment