Sulfate Conjugates as Solute Carrier Transporter Substrates; Probes, Biomarkers, and Utility?

Date: January 03 2017
Presenter(s): Dr. David Rodrigues

The Webinar was presented on 1 March, 2017 by Dr. David Rodrigues, Head of Transporter Sciences Group at Pfizer, Inc., Groton, US.

Summary: Sulfotransferases (SULTs) are expressed in numerous tissues and catalyze the sulfation of many steroidal drugs and endogenous compounds. Examples include 17α-ethinylestradiol, estrone, various bile acids, and dehydroepiandrosterone (DHEA). Once formed, sulfate conjugates present as transporter [solute carrier (SLC) and ATP-binding cassette (ABC)] substrates and are secreted into bile, circulate, and eliminated in urine. Consequently, attention has focused on the study of the “SULT-transporter axis” and vectorial (sequential SLC-ABC) transport of sulfo-conjugates in clearance organs like the intestine, liver and kidney. In particular, various groups have sort to identify, develop and validate individual sulfate conjugates as clinical biomarkers for different transporters; the availability of such tools could facilitate transporter phenotyping and drug-drug interaction assessment. For example, the 3-O-sulfate of DHEA (DHEAS) has been proposed as a hepatic OATP (organic anion transporting polypeptide) biomarker. Likewise, the 3-O-sulfate form of glycochenodeoxycholic acid (GCDCA-S) has been studied as a biomarker of renal OAT3 (organic anion transporter 3). Numerous groups have also deployed estrone 3-O-sulfate (E3S) as an OATP probe, which has supported relative activity factor-based SLC phenotyping in vitro. The webinar will focus on examples of steroidal sulfate conjugates as transporter substrates, probes, and potential biomarkers. As an uptake organ, the liver will be presented in terms of the “big seven” SLCs [OATP1B1, OATP1B3, OATP2B1, organic cation transporter 1 (OCT1), sodium-taurocholate co-transporting polypeptide (NTCP), OAT2, and OAT7].

Presenter: DAVID RODRIGUES, PH.D. Head of Transporter Sciences Group,Pfizer, Inc.


Dr. Rodrigues has been in the pharmaceutical industry for 26 years and now serves as Research Fellow at Pfizer (Pharmacokinetics, Dynamics & Metabolism Department; Groton, CT). He is head of the Transporter Sciences Group. Before joining Pfizer in April of 2014, he worked at various pharmaceutical companies (BMS, Merck, Abbott, and Searle); serving on both managerial (Director, Senior Director, and Executive Director) and research (Fellow) ladders. Prior to joining the pharmaceutical industry, Dr. Rodrigues studied in England and graduated with a B.Sc degree (Kingston-Upon-Thames Polytechnic, Kingston, Surrey) and a Ph.D (Surrey University, Guildford, Surrey). Upon graduation, he joined the laboratory of Dr. Russell Prough and conducted postdoctoral studies (University of Louisville School of Medicine, Louisville, KY). Dr. Rodrigues is interested in hypothesis-enabled, literature-driven, integrative and translational PK-ADME science, problem solving, and the discovery and development of new chemical entities. He has (co-) authored nearly 20 different book chapters, over 120 peer-reviewed manuscripts, and has presented at over 60 symposia/meetings. Dr. Rodrigues is an AAPS Fellow and has served on the ISSX Scientific Affairs Committee. He has also served on the Editorial Board of numerous drug metabolism journals, is currently Associate Editor of Xenobiotica, and has edited/co-edited 4 books (3 related to drug interactions and one on the topic of drug metabolism). Since the summer of 2014, Dr. Rodrigues has also served as an adjunct professor at the University of Rhode Island, School of Pharmacy.