Literature DB >> 24944729

Validity of ligand efficiency metrics.

Christopher W Murray1, Daniel A Erlanson2, Andrew L Hopkins3, György M Keserü4, Paul D Leeson5, David C Rees1, Charles H Reynolds6, Nicola J Richmond5.   

Abstract

A recent viewpoint article (Improving the plausibility of success with inefficient metrics. ACS Med. Chem. Lett. 2014, 5, 2-5) argued that the standard definition of ligand efficiency (LE) is mathematically invalid. In this viewpoint, we address this criticism and show categorically that the definition of LE is mathematically valid. LE and other metrics such as lipophilic ligand efficiency (LLE) can be useful during the multiparameter optimization challenge faced by medicinal chemists.

Year:  2014        PMID： 24944729      PMCID： PMC4060940          DOI： 10.1021/ml500146d

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  11 in total

Review 1.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.

Authors:  C A Lipinski; F Lombardo; B W Dominy; P J Feeney
Journal:  Adv Drug Deliv Rev       Date:  2001-03-01       Impact factor: 15.470

2.  Ligand efficiency: a useful metric for lead selection.

Authors:  Andrew L Hopkins; Colin R Groom; Alexander Alex
Journal:  Drug Discov Today       Date:  2004-05-15       Impact factor: 7.851

Review 3.  The influence of drug-like concepts on decision-making in medicinal chemistry.

Authors:  Paul D Leeson; Brian Springthorpe
Journal:  Nat Rev Drug Discov       Date:  2007-11       Impact factor: 84.694

4.  Simple size-independent measure of ligand efficiency.

Authors:  J Willem M Nissink
Journal:  J Chem Inf Model       Date:  2009-06       Impact factor: 4.956

Review 5.  The influence of lead discovery strategies on the properties of drug candidates.

Authors:  György M Keserü; Gergely M Makara
Journal:  Nat Rev Drug Discov       Date:  2009-03       Impact factor: 84.694

6.  Setting expectations in molecular optimizations: Strengths and limitations of commonly used composite parameters.

Authors:  Michael D Shultz
Journal:  Bioorg Med Chem Lett       Date:  2013-08-13       Impact factor: 2.823

7.  Ligand binding efficiency: trends, physical basis, and implications.

Authors:  Charles H Reynolds; Brett A Tounge; Scott D Bembenek
Journal:  J Med Chem       Date:  2008-04-02       Impact factor: 7.446

8.  Assessing the lipophilicity of fragments and early hits.

Authors:  Paul N Mortenson; Christopher W Murray
Journal:  J Comput Aided Mol Des       Date:  2011-05-26       Impact factor: 3.686

Review 9.  The role of ligand efficiency metrics in drug discovery.

Authors:  Andrew L Hopkins; György M Keserü; Paul D Leeson; David C Rees; Charles H Reynolds
Journal:  Nat Rev Drug Discov       Date:  2014-02       Impact factor: 84.694

10.  Improving the plausibility of success with inefficient metrics.

Authors:  Michael D Shultz
Journal:  ACS Med Chem Lett       Date:  2013-11-21       Impact factor: 4.345
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  19 in total

1.  Homology models of mouse and rat estrogen receptor-α ligand-binding domain created by in silico mutagenesis of a human template: molecular docking with 17ß-estradiol, diethylstilbestrol, and paraben analogs.

Authors:  Thomas L Gonzalez; James M Rae; Justin A Colacino; Rudy J Richardson
Journal:  Comput Toxicol       Date:  2018-11-28

2.  Computer-aided drug discovery research at a global contract research organization.

Authors:  Douglas B Kitchen
Journal:  J Comput Aided Mol Des       Date:  2016-11-01       Impact factor: 3.686

3.  Ligand efficiency metrics considered harmful.

Authors:  Peter W Kenny; Andrei Leitão; Carlos A Montanari
Journal:  J Comput Aided Mol Des       Date:  2014-06-05       Impact factor: 3.686

4.  The twin drug approach for novel nicotinic acetylcholine receptor ligands.

Authors:  Isabelle Tomassoli; Daniela Gündisch
Journal:  Bioorg Med Chem       Date:  2015-06-20       Impact factor: 3.641

5.  Optimization of a 1,3,4-oxadiazole series for inhibition of Ca2+/calmodulin-stimulated activity of adenylyl cyclases 1 and 8 for the treatment of chronic pain.

Authors:  Jatinder Kaur; Monica Soto-Velasquez; Zhong Ding; Ahmadreza Ghanbarpour; Markus A Lill; Richard M van Rijn; Val J Watts; Daniel P Flaherty
Journal:  Eur J Med Chem       Date:  2018-11-16       Impact factor: 6.514

6.  Computational prediction and validation of an expert's evaluation of chemical probes.

Authors:  Nadia K Litterman; Christopher A Lipinski; Barry A Bunin; Sean Ekins
Journal:  J Chem Inf Model       Date:  2014-10-07       Impact factor: 4.956

7.  Optimizing Ligand Efficiency of Selective Androgen Receptor Modulators (SARMs).

Authors:  Anthony L Handlon; Lee T Schaller; Lisa M Leesnitzer; Raymond V Merrihew; Chuck Poole; John C Ulrich; Joseph W Wilson; Rodolfo Cadilla; Philip Turnbull
Journal:  ACS Med Chem Lett       Date:  2015-11-19       Impact factor: 4.345

Review 8.  Protein crystallography and drug discovery: recollections of knowledge exchange between academia and industry.

Authors:  Tom L Blundell
Journal:  IUCrJ       Date:  2017-06-29       Impact factor: 4.769

9.  Beware of ligand efficiency (LE): understanding LE data in modeling structure-activity and structure-economy relationships.

Authors:  Jaroslaw Polanski; Aleksandra Tkocz; Urszula Kucia
Journal:  J Cheminform       Date:  2017-09-11       Impact factor: 5.514

10.  In silico analysis of natural compounds targeting structural and nonstructural proteins of chikungunya virus.

Authors:  Jaspreet Jain; Anchala Kumari; Pallavi Somvanshi; Abhinav Grover; Somnath Pai; Sujatha Sunil
Journal:  F1000Res       Date:  2017-08-30
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