@article{0801e0d7d2324d60acc318a0163f9862,
title = "Bayesian models leveraging bioactivity and cytotoxicity information for drug discovery",
abstract = "Identification of unique leads represents a significant challenge in drug discovery. This hurdle is magnified in neglected diseases such as tuberculosis. We have leveraged public high-throughput screening (HTS) data to experimentally validate a virtual screening approach employing Bayesian models built with bioactivity information (single-event model) as well as bioactivity and cytotoxicity information (dual-event model). We virtually screened a commercial library and experimentally confirmed actives with hit rates exceeding typical HTS results by one to two orders of magnitude. This initial dual-event Bayesian model identified compounds with antitubercular whole-cell activity and low mammalian cell cytotoxicity from a published set of antimalarials. The most potent hit exhibits the in vitro activity and in vitro/in vivo safety profile of a drug lead. These Bayesian models offer significant economies in time and cost to drug discovery.",
author = "Sean Ekins and Reynolds, {Robert C.} and Hiyun Kim and Koo, {Mi Sun} and Marilyn Ekonomidis and Meliza Talaue and Paget, {Steve D.} and Woolhiser, {Lisa K.} and Lenaerts, {Anne J.} and Bunin, {Barry A.} and Nancy Connell and Freundlich, {Joel S.}",
note = "Funding Information: Accelrys is kindly acknowledged for providing Discovery Studio (to S.E.). We acknowledge Dr. Eric L. Nuermberger (Johns Hopkins University) for valuable discussions. The CDD TB database has been developed thanks to funding from the Bill and Melinda Gates Foundation (grant no. 49852, “Collaborative Drug Discovery for TB through a Novel Database of SAR Data Optimized to Promote Data Archiving and Sharing”). The project described was supported by award no. R43 LM011152-01, “Biocomputation across Distributed Private Datasets to Enhance Drug Discovery” from the National Library of Medicine. R.C.R. acknowledges American Reinvestment and Recovery Act grant no. 1RC1AI086677-01 (National Institute of Allergy and Infectious Diseases [NIAID], National Institutes of Health), “Targeting MDR-TB”. J.S.F. acknowledges funding from New Jersey Medical School, University of Medicine and Dentistry of New Jersey (UMDNJ) and the Foundation of UMDNJ. A.J.L. is grateful for support through TB contract no. N01 Al-95385 (NIAID Project through Dr. Tina Parker). S.E. is a consultant for Collaborative Drug Discovery, Inc. B.A.B. is an employee and shareholder of Collaborative Drug Discovery, Inc. ",
year = "2013",
month = mar,
day = "21",
doi = "10.1016/j.chembiol.2013.01.011",
language = "English (US)",
volume = "20",
pages = "370--378",
journal = "Chemistry and Biology",
issn = "1074-5521",
publisher = "Elsevier Inc.",
number = "3",
}