Validity of ligand efficiency metrics

ACS Medicinal Chemistry Letters

Volumn 5, Issue 6, 2014, Pages 616-618

  Murray, Christopher W ^a   Erlanson, Daniel A ^b   Hopkins, Andrew L ^c   Keserü, György M ^d   Leeson, Paul D ^e   Rees, David C ^a   Reynolds, Charles H ^f   Richmond, Nicola J ^d  

^a ASTEX PHARMACEUTICALS   (United Kingdom)

^b Carmot Therapeutics Inc   (United States)

^c UNIVERSITY OF DUNDEE   (United Kingdom)

^d INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

^e GLAXOSMITHKLINE   (United Kingdom)

^f Gfree Bio LLC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LIGAND;

ARTICLE; CHEMICAL STRUCTURE; LIGAND EFFICIENCY METRICS; MATHEMATICAL PARAMETERS; PRIORITY JOURNAL; VALIDITY;

EID: 84902499723     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml500146d     Document Type: Article

References (12)

1. Shultz, M. D. Improving the plausibility of success with inefficient metrics ACS Med. Chem. Lett. 2014, 5, 2-5
2. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings Adv. Drug Delivery Rev. 2001, 46, 3-26
3. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand efficiency: a useful metric for lead selection Drug Discovery Today 2004, 9, 430-431
4. Kuntz, I. D.; Chen, K.; Sharp, K. A.; Kollman, P. A. The maximal affinity of ligands Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 9997-10002
5. Shultz, M. D. Setting expectations in molecular optimizations: Strengths and limitations of commonly used composite parameters Bioorg. Med. Chem. Lett. 2013, 23, 5980-5991
6. LE is a mathematically well-defined function f = R × N → R that maps the Cartesian product space domain of reals and positive integers to the codomain of reals. For a definition of a function, see Haaser, N. B.; Sullivan, J. A. Real Analysis; Dover: Mineola, NY, 1991.
7. Leeson, P. D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry Nat. Rev. Drug Discovery 2007, 6, 881-890
8. Reynolds, C. H.; Tounge, B. A.; Bembenek, S. D. Ligand binding efficiency: trends, physical basis, and implications J. Med. Chem. 2008, 51, 2432-2438
9. Nissink, J. W. M. Simple size-independent measure of ligand efficiency J. Chem. Inf. Model. 2009, 49, 1617-1622
10. Hopkins, A. L.; Keserü, G. M.; Leeson, P. D.; Rees, D. C.; Reynolds, C. H. The role of ligand efficiency metrics in drug discovery Nat. Rev. Drug Discovery 2014, 13, 105-121
11. Keserü, G. M.; Makara, G. M. The influence of lead discovery strategies on the properties of candidates Nat. Rev. Drug Discovery 2009, 8, 203-212
12. Mortenson, P. N.; Murray, C. W. Assessing the lipophilicity of fragments and early hits J. Comput.-Aided. Mol. Des. 2011, 25, 663-667