Accelerating Lead Identification by High Throughput Virtual Screening: Prospective Case Studies from the Pharmaceutical Industry

Journal of Chemical Information and Modeling
Kelly L Damm-GanametTaraneh Mirzadegan

Abstract

At the onset of a drug discovery program, the goal is to identify novel compounds with appropriate chemical features that can be taken forward as lead series. Here, we describe three prospective case studies, Bruton Tyrosine Kinase (BTK), RAR-Related Orphan Receptor γ t (RORγt), and Human Leukocyte Antigen DR isotype (HLA-DR) to illustrate the positive impact of high throughput virtual screening (HTVS) on the successful identification of novel chemical series. Each case represents a project with a varying degree of difficulty due to the amount of structural and ligand information available internally or in the public domain to utilize in the virtual screens. We show that HTVS can be effectively employed to identify a diverse set of potent hits for each protein system even when the gold standard, high resolution structural data or ligand binding data for benchmarking, is not available.

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Citations

Aug 17, 2019·Current Topics in Medicinal Chemistry·Sheisi F L da Silva RochaCarlos M R Sant'Anna
Nov 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lei ZhaoXingzhou Li
Feb 5, 2021·European Journal of Pharmacology·Krishnaprasad BabyYogendra Nayak
Jan 9, 2020·Journal of Medicinal Chemistry·Kelly L Damm-GanametTaraneh Mirzadegan
Apr 21, 2020·Journal of Chemical Information and Modeling·Xin Cindy YanHarold B Wood
Apr 17, 2020·Journal of Medicinal Chemistry·Henriëtte WillemsFredrik Svensson
Aug 23, 2019·ACS Combinatorial Science·Olena SavychOleksandr O Grygorenko
May 28, 2019·Journal of Chemical Information and Modeling·Habibah A WahabZoe Cournia

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