Literature DB >> 24900765

Improving the plausibility of success with inefficient metrics.

Michael D Shultz1.   

Abstract

To increase the probability of success in drug discovery, the concept of drug-like properties was introduced. Efficiency metrics that normalize potency against these properties could help reach drug-like space more efficiently. Potential reasons for the inefficient use of metrics and suboptimal decision making are discussed.

Keywords:  Ligand efficiency (LE); decision making; drug-likeness; efficiency metrics; fragment-based drug design; lipophilic efficiency (LipE)

Year:  2013        PMID： 24900765      PMCID： PMC4027587          DOI： 10.1021/ml4004638

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


  7 in total

1.  A comparison of physiochemical property profiles of development and marketed oral drugs.

Authors:  Mark C Wenlock; Rupert P Austin; Patrick Barton; Andrew M Davis; Paul D Leeson
Journal:  J Med Chem       Date:  2003-03-27       Impact factor: 7.446

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

3.  Medicinal chemistry matters - a call for discipline in our discipline.

Authors:  Craig Johnstone
Journal:  Drug Discov Today       Date:  2012-01-25       Impact factor: 7.851

4.  Relating molecular properties and in vitro assay results to in vivo drug disposition and toxicity outcomes.

Authors:  Jeffrey J Sutherland; John W Raymond; James L Stevens; Thomas K Baker; David E Watson
Journal:  J Med Chem       Date:  2012-07-05       Impact factor: 7.446

5.  The thermodynamic basis for the use of lipophilic efficiency (LipE) in enthalpic optimizations.

Authors:  Michael D Shultz
Journal:  Bioorg Med Chem Lett       Date:  2013-08-14       Impact factor: 2.823

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.  Inflation of correlation in the pursuit of drug-likeness.

Authors:  Peter W Kenny; Carlos A Montanari
Journal:  J Comput Aided Mol Des       Date:  2013-01-10       Impact factor: 3.686
  7 in total
  9 in total

1.  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

2.  Validity of ligand efficiency metrics.

Authors:  Christopher W Murray; Daniel A Erlanson; Andrew L Hopkins; György M Keserü; Paul D Leeson; David C Rees; Charles H Reynolds; Nicola J Richmond
Journal:  ACS Med Chem Lett       Date:  2014-05-09       Impact factor: 4.345

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.  Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2.

Authors:  Christopher G Nasveschuk; Alexandre Gagnon; Shivani Garapaty-Rao; Srividya Balasubramanian; Robert Campbell; Christina Lee; Feng Zhao; Louise Bergeron; Richard Cummings; Patrick Trojer; James E Audia; Brian K Albrecht; Jean-Christophe P Harmange
Journal:  ACS Med Chem Lett       Date:  2014-01-14       Impact factor: 4.345

5.  Drug-likeness approach of 2-aminopyrimidines as histamine H3 receptor ligands.

Authors:  Bassem Sadek; Annemarie Schreeb; Johannes Stephan Schwed; Lilia Weizel; Holger Stark
Journal:  Drug Des Devel Ther       Date:  2014-09-19       Impact factor: 4.162

6.  Combining organometallic reagents, the sulfur dioxide surrogate DABSO, and amines: a one-pot preparation of sulfonamides, amenable to array synthesis.

Authors:  Alex S Deeming; Claire J Russell; Michael C Willis
Journal:  Angew Chem Int Ed Engl       Date:  2014-11-27       Impact factor: 15.336

7.  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

8.  Synthesis, Molecular Properties Estimations, and Dual Dopamine D2 and D3 Receptor Activities of Benzothiazole-Based Ligands.

Authors:  Moritz Schübler; Bassem Sadek; Tim Kottke; Lilia Weizel; Holger Stark
Journal:  Front Chem       Date:  2017-09-12       Impact factor: 5.221

9.  Apigenin and Structurally Related Flavonoids Allosterically Potentiate the Function of Human α7-Nicotinic Acetylcholine Receptors Expressed in SH-EP1 Cells.

Authors:  Waheed Shabbir; Keun-Hang Susan Yang; Bassem Sadek; Murat Oz
Journal:  Cells       Date:  2021-05-05       Impact factor: 6.600
  9 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.