Implications of endogenous roles of transporters for drug discovery: Hitchhiking and metabolite-likeness

Nature Reviews Drug Discovery

Volumn 15, Issue 2, 2016, Pages 143-144

  Kell, Douglas B ^a  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; CARRIER PROTEIN; SEPANTRONIUM BROMIDE; SOLUTE CARRIER TRANSPORTER; UNCLASSIFIED DRUG; DRUG;

BINDING AFFINITY; BINDING SITE; CELL MEMBRANE PERMEABILITY; DRUG DEVELOPMENT; DRUG IDENTIFICATION; DRUG SCREENING; DRUG TOXICITY; DRUG UPTAKE; HITCHHIKING LIKENESS; HUMAN; LETTER; MEDICAL LITERATURE; METABOLITE LIKENESS; MOLECULAR BIOLOGY; MOLECULAR MODEL; NATURAL SELECTION; NONHUMAN; PHOSPHOLIPID BILAYER; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; STRUCTURAL MODELING; ANIMAL; METABOLISM; PROCEDURES; TRENDS;

ANIMALS; DRUG DISCOVERY; HUMANS; MEMBRANE TRANSPORT PROTEINS; PHARMACEUTICAL PREPARATIONS;

EID: 84957885675     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd.2015.44     Document Type: Letter

References (10)

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3. Dobson, P. D., & Kell, D. B. Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule? Nat. Rev. Drug Discov. 7, 205-220 (2008
4. Kell, D. B., & Oliver, S. G. How drugs get into cells: tested and testable predictions to help discriminate between transporter-mediated uptake and lipoidal bilayer diffusion. Front. Pharmacol. 5, 231 (2014
5. Winter G. E., et al. The solute carrier SLC35F2 enables YM155 mediated DNA damage toxicity. Nat. Chem. Biol. 10, 768-773 (2014
6. Kell, D. B. Finding novel pharmaceuticals in the systems biology era using multiple effective drug targets, phenotypic screening, and knowledge of transporters: where drug discovery went wrong and how to fix it. FEBS J. 280, 5957-5980 (2013
7. O Hagan, S., Swainston, N., Handl, J., & Kell, D. B. A rule of 0.5 for the metabolite-likeness of approved pharmaceutical drugs. Metabolomics 11 323-339 2015
8. Jayaseelan, K. V., Moreno, P., Truszkowski, A., Ertl, P., & Steinbeck, C. Natural product-likeness score revisited: an open-source, open-data implementation. BMC Bioinformatics 13, 106 (2012
9. O Hagan, S., & Kell, D. B. The apparent permeabilities of Caco 2 cells to marketed drugs: magnitude, and independence from both biophysical properties and endogenite similarities. PeerJ. 3, e1405 (2015
10. Mendes, P., Oliver, S. G., & Kell, D. B. Fitting transporter activities to cellular drug concentrations and fluxes: why the bumblebee can fly. Trends Pharmacol. Sci. 36, 710-723 (2015