Impact of FDA-Approved Drugs on the Prostaglandin Transporter OATP2A1/SLCO2A1

J Pharm Sci. 2017 Sep;106(9):2483-2490. doi: 10.1016/j.xphs.2017.04.046. Epub 2017 May 4.


To understand interaction of drugs with the prostaglandin transporter OATP2A1/SLCO2A1 that regulates disposition of prostaglandins, we explored the impact of 636 drugs in an FDA-approved drug library on 6-carboxyfluorescein (6-CF) uptake by OATP2A1-expressing HEK293 cells (HEK/2A1). Fifty-one and 10 drugs were found to inhibit and enhance 6-CF uptake by more than 50%, respectively. Effect of the 51 drugs on 6-CF uptake was positively correlated with that on PGE2 uptake (r = 0.64, p < 0.001). Among those, 5 drugs not structurally related to prostaglandins, suramin, pranlukast, zafirlukast, olmesartan medoxomil, and losartan potassium, exhibited more than 90% PGE2 uptake inhibition. Inhibitory affinity of suramin to OATP2A1 was the highest (IC50,2A1 of 0.17 μM), and its IC50 values to MRP4-mediated PGE2 transport (IC50,MRP4) and PGE2 synthesis in human U-937 cells treated with phorbol 12-myristate 13-acetate (IC50,Syn) were 73.6 and 336.7 times higher than IC50,2A1, respectively. Moreover, structure-activity relationship study in 29 nonsteroidal anti-inflammatory drugs contained in the library displayed inhibitory activities of anthranilic acid derivatives, but enhancing effects of propionic acid derivatives. These results demonstrate that suramin is a potent selective inhibitor of OATP2A1, providing a comprehensive information about drugs in clinical use that interact with OATP2A1.

Keywords: drug effects; organic anion-transporting polypeptide transporters; pharmacodynamics; pharmacokinetics; structure-activity relationship (SAR); transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antineoplastic Agents / pharmacology
  • Biological Transport / drug effects*
  • Cell Line
  • Fluoresceins / metabolism
  • HEK293 Cells
  • Humans
  • Organic Anion Transporters / antagonists & inhibitors*
  • Organic Anion Transporters / metabolism*
  • Prostaglandins / metabolism
  • Structure-Activity Relationship
  • Suramin / pharmacology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Fluoresceins
  • Organic Anion Transporters
  • Prostaglandins
  • SLCO2A1 protein, human
  • 6-carboxyfluorescein
  • Suramin