369
Views
3
CrossRef citations to date
0
Altmetric
Review

Ligand efficiency indices for effective drug discovery: a unifying vector formulation

Pages 763-775 | Received 02 Dec 2020, Accepted 28 Jan 2021, Published online: 11 Mar 2021

References

  • Hopkins AL, Groom CR, Alex A. Ligand efficiency: a useful metric for lead selection. Drug Discov Today. 2004;9(10):430–431.
  • Abad-Zapatero, C. Ligand Efficiency Indices for effective drug discovery. Expert Opin Drug Discov. 2007;2(4):469–488.
  • Shultz MD. Improving the plausibility of success with inefficient metrics. ACS Med Chem Lett. 2013;5(1):2–5.
  • Sheridan RP. Debunking the idea that ligand efficiency indices are superior to pIC50 as QSAR activities. J Chem Inf Model. 2016;56(11):2253–2262.
  • Cavalluzzi MM, Mangiatordi GF, Nicolotti O, et al. Ligand efficiency metrics in drug discovery: the pros and cons from a practical perspective. Expert Opin Drug Discov. 12(11): 1087–1104. 2017; .
  • Abad-Zapatero C, Champness EJ, Segall MD. Alternative variables in drug discovery: promises and challenges. Future Med Chem. 2014;6(5):577–593.
  • Abad-Zapatero C, Metz JM. Ligand efficiency indices as guideposts for drug discovery. Drug Discov Today. 2005;10(7):464–469.
  • Abad-Zapatero C, Perisic O, Wass J J, et al. Ligand efficiency indices for an effective mapping of chemico-biological space: the concept of an atlas-like representation. Drug Discov Today. 15(19–20): 804–811. 2010; .
  • Abad-Zapatero C. Ligand efficiency indices for drug discovery. Towards an Atlas-Guided Paradigm: Elsevier; 2013. .
  • Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov. 2007;6(11):881–890.
  • Hopkins AL, Keseru GM, Leeson PD, et al. The role of ligand efficiency metrics in drug discovery. Nat Rev Drug Discov. 13(2): 105–121. 2014; .
  • Shultz MD. Improving the plausibility of success with inefficient metrics. ACS Med Chem Lett. 2014;5(1):2–5.
  • Reynolds CH, Bembenek SD, Tounge BA. The role of molecular size in ligand efficiency. Bioorg Med Chem Lett. 2007;17(15):4258–4261.
  • Reynolds CH, Holloway KM. Thermodynamics of ligand binding and efficiency. ACS Med Chem Lett. 2011;2:433–437.
  • Willem J, Nissink JW. Simple size-independent measure of ligand efficiency. J Chem Inf Model. 2009;49(6):1617–1622.
  • Hajduk PJ. Fragment-based drug design: how big is too big? J Med Chem. 2006;49(24):6972–6976.
  • Cortés-Cabrera A, Morreale A, Gago F, et al. AtlasCBS: a web server to map and explore chemico-biological space. J Comput Aided Mol Des. 2012;26(9):995–1003.
  • Abad-Zapatero C. AtlasCBS: a graphic tool to map the content of structure-activity dabases. In: Mukhametov A, editor. Software and techniques for bio-molecular modelling. Austin Publishing Group. 2016. p. 19–37.
  • Davies M, Nowotka M, Papadatos G, et al. MyCHEMBL: a virtual platform for distributing cheminformatics tools and open data. Challenges. 5(2): 334–337. 2014; .
  • Ochoa R, Davies M, Papadatos G, et al. myChEMBL: a virtual machine implementation of open data and cheminformatics tools. Bioinformatics. 30(2): 298–300. 2014; .
  • Alvarez-Carretero S, Pavlopoulou N, Adams J, et al. VSpipe, an integrated resource for virtual screening and hit selection: applications to protein tyrosine phospahatase inhibition. Molecules. 23(2): 2. 2018; .
  • Cotrina EY, Blasi D, Vila M, et al. Optimization of kinetic stabilizers of tetrameric transthyretin: a prospective ligand efficiency-guided approach. Bioorg Med Chem. 28(23): 115794. 2020; .
  • Segall M, Champness E, Leeding C, et al. Applying medicinal chemistry transformations and multiparameter optimization to guide the search for high-quality leads and candidates. J Chem Inf Model. 51(11): 2967–2976. 2011; .
  • Moult J, Hubbard T, Fidelis K, et al. Critical assessment of methods of protein structure prediction (CASP): round III. Proteins. 1999;(Suppl 3):2–6.
  • Gaieb Z, Liu S, Gathiaka S, et al. D3R grand challenge 2: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies. J Comput Aided Mol Des. 32(1): 1–20. 2018; .
  • Perola E. An analysis of the binding efficiencies of drugs and their leads in successful drug discovery programs. J Med Chem. 2010;53(7):2986–2997.
  • Abad-Zapatero C, Blasi D. Ligand efficiency indices (LEIs): more than a simple efficiency yardstick. Mol Inform. 2011;30(2–3):122–132.
  • Stewart KD, Shiroda M, James CA. Drug guru: a computer software program for drug design using medicinal chemistry rules. Bioorg Med Chem. 2006;14(20):7011–7022.
  • Senior AW, Evans R, Jumper J, et al. Improved protein structure prediction using potentials from deep learning. Nature. 577(7792): 706–710. 2020; .
  • Abad-Zapatero, C. Are SAR tables obsolete? Drug Discov Today. 2017;22(2):195–198.
  • Lavoisier A Oeuvres, 1785.
  • Kim MG. Affinity, that elusive dream. A Genealogy of the Chemical Revolution. Cambridge. Mass: The MIT Press; 2003.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.