Lead-like, drug-like or "Pub-like": how different are they?

Lead-like, drug-like or "Pub-like": how different are they? Research Abstract Details 

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Lead-like, drug-like or "Pub-like": how different are they? Abstract Text:

Tudor I Oprea,Tharun Kumar Allu,Dan C Fara,Ramona F Rad,Lili Ostopovici,Cristian G Bologa,

Academic and industrial research continues to be focused on discovering new classes of compounds based on HTS. Post-HTS analyses need to prioritize compounds that are progressed to chemical probe or lead status. We report trends in probe, lead and drug discovery by examining the following categories of compounds: 385 leads and the 541 drugs that emerged from them; "active" (152) and "inactive" (1488) compounds from the Molecular Libraries Initiative Small Molecule Repository (MLSMR) tested by HTS; "active" (46) and "inactive" (72) compounds from Nature Chemical Biology (NCB) tested by HTS; compounds in the drug development phase (I, II, III and launched), as indexed in MDDR; and medicinal chemistry compounds from WOMBAT, separated into high-activity (5,784 compounds with nanomolar activity or better) and low-activity (30,690 with micromolar activity or less). We examined Molecular weight (MW), molecular complexity, flexibility, the number of hydrogen bond donors and acceptors, LogP-the octanol/water partition coefficient estimated by ClogP and ALOGPS), LogSw (intrinsic water solubility, estimated by ALOGPS) and the number of Rule of five (Ro5) criteria violations. Based on the 50% and 90% distribution moments of the above properties, there were no significant difference between leads of known drugs and "actives" from MLSMR or NCB (chemical probes). "Inactives" from NCB and MLSMR were also found to exhibit similar properties. From these combined sets, we conclude that "Actives" (569 compounds) are less complex, less flexible, and more soluble than drugs (1,651 drugs), and significantly smaller, less complex, less hydrophobic and more soluble than the 5,784 high-activity WOMBAT compounds. These trends indicate that chemical probes are similar to leads with respect to some properties, e.g., complexity, solubility, and hydrophobicity.

Lead-like, drug-like or "Pub-like": how different are they? Publishing Authors By Initials

TI Oprea,TK Allu,DC Fara,RF Rad,L Ostopovici,CG Bologa,

For similar chemical and pharmacologic phenomena: drug design research abstracts see: chemical and pharmacologic phenomena: drug design research

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Lead-like, drug-like or "Pub-like": how different are they? Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of computer-aided molecular design

VOLUME: 21

Page Numbers: 113-9

Journal Abbreviation: J. Comput. Aided Mol. Des.

ISSN: 0920-654X

DAY: 28

MONTH: 02

YEAR: 2007

Lead-like, drug-like or "Pub-like": how different are they? Information

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LANGUAGE: eng

NlmUniqueID: 8710425

Lead-like, drug-like or "Pub-like": how different are they? Keywords Mesh Terms:

KEYWORDS: Drug Design

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Grant and Affiliation Information for Lead-like, drug-like or "Pub-like": how different are they?

AFFILIATION: Division of Biocomputing, Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, MSC11 6145, Albuquerque, NM 87131, USA. TOprea@salud.unm.edu

Country: Netherlands

AGENCY: United States NIMH

GRANT: U54 MH074425-01

ACRONYM: MH

MEDLINETA: J Comput Aided Mol Des

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