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].

About the presenter:


Senior Scientific Director, Head of the Transporter Sciences Group,  Pfizer (ADME Sciences, Medicine Design) Groton, CT


David has been in the pharmaceutical industry for 32 years and currently holds the title of Senior Scientific Director as head of the Transporter Sciences Group at Pfizer (Groton, CT, USA).  Before joining Pfizer in 2014, he spent productive periods at other US-based pharmaceutical companies (Searle, Abbott Labs, Merck, and Bristol-Myers Squibb).  During that time, he served on both scientific and managerial ladders.  He has authored 179 peer-reviewed manuscripts, presented >85 seminars/talks/webinars, and in the past served on the editorial boards of various DMPK-related journals (Xenobiotica, Drug Metabolism & Disposition, Current Drug Metabolism). In addition, he has edited/co-edited four DMPK-related textbooks.  Presently, he serves as adjunct professor at the College of Pharmacy, University of Rhode Island, and is a member of the International Transporter Consortium (ITC). In 2009, David was inducted as Fellow of The American Association of Pharmaceutical Scientists (AAPS).  He is the recipient of the 2021 Distinguished Accomplishments in Drug Discovery & Development Award bestowed by the International Society for the Study of Xenobiotics (ISSX).