Transporter Pharmacophores

The human genome contains nearly 900 genes that encode transporters, of which over 300 are intracellular transporters [1] responsible for transporting a wide range of molecules across the membrane [2]. Further classification of these transporters into families such as the solute carrier dass (SLC) [3] and ATP binding cassette (ABC) family 4, 5] is possible. Transporters play a major role in clinical pharmacology as their adequate bioavailability determines the successful oral delivery of many therapeutics. Membrane transporter proteins are associated with drug absorption (uptake), tissue distribution (efflux and uptake), metabolism (hepatic efflux and uptake), and elimination (renal, biliary transporters, and breast milk efflux and uptake) [6, 7]. 

What is a pharmacophore Paul Ehrlich defined a pharmacophore as a molecular framework that carries (phoros) the essential features responsible for 

Organic anion transporter polypeptides OATP (SLC21A family) [30] 

Sodium taurocholate cotransporting NTCP (SLClOA family) [76] 

Apical sodium-dependent bile acid ASBT (SLC10A2) [77, 78] 

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P-gp substrate 9 substrates and 69 substrates and 88.4% substrates Transport and Caco-2 (transport) Pharmacophore (sub- [54]... 

Figure 8.1 Schematic of database screening with transporter pharmacophores.

Chang C, Pang KS, Swaan PW, Ekins S. Comparative pharmacophore modeling of organic anion transporting polypeptides a meta-analysis of rat Oatplal and human OATPIBI. J Pharmacol Exp Ther 2005 314 533-41. 

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