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. Author manuscript; available in PMC: 2021 Jul 1.
Published in final edited form as: Pharmacol Ther. 2020 Apr 2;211:107542. doi: 10.1016/j.pharmthera.2020.107542

Table 4.

In Vitro Substrates of OSTα/β and Other Transporters.

OSTα/β Substrate OSTα/β Km (μM) OSTα/β-expressing System Also a Substrate for These Transporters References
1. Bile Acids
CA >400* MDCKII-transfected NTCP, ASBT, OATP1B1, OATP1B3, MRP4, BCRP (Balakrishnan, Wring, & Polli, 2006; Blazquez, et al., 2012; Craddock, et al., 1998; Cui, Konig, Leier, Buchholz, & Keppler, 2001; Dong, Ekins, & Polli, 2015; Ho, Leake, Roberts, Lee, & Kim, 2004; Rius, Hummel-Eisenbeiss, Hofmann, & Keppler, 2006; Suga, et al., 2019; Suga, et al., 2017)
CDCA 23.0 MDCKII-transfected OATP1B1, OATP1B3 (Suga, et al., 2019; Suga, et al., 2017)
DCA 14.9 MDCKII-transfected OATP1B1, OATP1B3 (Suga, et al., 2019; Suga, et al., 2017)
GCA >1,000* MDCK-transfected; MDCKII-transfected NTCP, ASBT, OATP1B1, OATP1B3, BSEP, MRP3, MRP4, BCRP (Balakrishnan, et al., 2006; Ballatori, et al., 2005; Blazquez, et al., 2012; Hayashi, et al., 2005; Kramer, et al., 1999; Meier, Eckhardt, Schroeder, Hagenbuch, & Stieger, 1997; Rius, et al., 2006; Suga, et al., 2019; Suga, et al., 2017; Zeng, Liu, Rea, & Kruh, 2000)
GCDCA 864.2 MDCK-transfected; MDCKII-transfected NTCP, ASBT, OATP1B1, OAT 1B3, MRP4, BSEP (Balakrishnan, et al., 2006; Ballatori, et al., 2005; Craddock, et al., 1998; Dong, et al., 2015; Hayashi, et al., 2005; Rius, et al., 2006; Suga, et al., 2019; Suga, et al., 2017)
GDCA 586.4 MDCK-transfected, MDCKII-transfected ASBT, OATP1B1, OATP1B3, MRP4 (Balakrishnan, et al., 2006; Ballatori, et al., 2005; Craddock, et al., 1998; Rius, et al., 2006; Suga, et al., 2019; Suga, et al., 2017)
GLCA 12.8 MDCKII-transfected NTCP, ASBT, OATP1B1, OATP1B3 (Balakrishnan, et al., 2006; Dong, et al., 2015; Suga, et al., 2019; Suga, et al., 2017)
GUDCA >1,000* MDCK-transfected, MDCKII-transfected NTCP, ASBT, OATP1B1, OATP1B3, BSEP, MRP4 (Balakrishnan, et al., 2006; Ballatori, et al., 2005; Craddock, et al., 1998; Dong, et al., 2015; Hayashi, et al., 2005; Maeda, Kambara, Tian, Hofmann, & Sugiyama, 2006; Rius, et al., 2006; Suga, et al., 2019; Suga, et al., 2017)
LCA NA MDCKII-transfected - (Suga, et al., 2019)
TCA 351–698; >10,000* X. laevis oocytes-injected, MDCK-transfected, HeLa-transfected; COS-transfected; Flp-In 293-transfected; MDCK-transfected; MDCKII-transfected NTCP, ASBT, OAT3, OATP1A2, OATP1B1, OATP1B3, OATP2B1, BSEP, MRP3, MRP4, BCRP (Abe, et al., 2001; Balakrishnan, et al., 2006; Ballatori, et al., 2005; Blazquez, et al., 2012; Cha, et al., 2001; Choi, et al., 2011; Craddock, et al., 1998; Hallen, Bjorquist, Ostlund-Lindqvist, & Sachs, 2002; Hayashi, et al., 2005; Kim, et al., 1999; Kramer, et al., 1999; Leslie, Watkins, Kim, & Brouwer, 2007; Love, et al., 2001; Malinen, et al., 2018; Meier, et al., 1997; Nozawa, Imai, Nezu, Tsuji, & Tamai, 2004; Rius, et al., 2006; Seward, et al., 2003; Suga, et al., 2019; Suga, et al., 2017; Sultan, et al., 2018; van de Wiel, et al., 2018; Visser, et al., 2010; Wang, et al., 2001; Zhang, et al., 2003)
TCDCA 723.7 MDCK-transfected; MDCKII-transfected NTCP, ASBT, OATP1B1, OATP1B3, MRP4, BSEP (Balakrishnan, et al., 2006; Ballatori, et al., 2005; Dong, et al., 2015; Kis, et al., 2009; Kramer, et al., 1999; Meier, et al., 1997; Rius, et al., 2006; Suga, et al., 2019; Suga, et al., 2017)
TDCA >2,000* MDCK-transfected, MDCKII-transfected ASBT, OATP1B1, OATP1B3, BSEP (Balakrishnan, et al., 2006; Ballatori, et al., 2005; Hayashi, et al., 2005; Kramer, et al., 1999; Suga, et al., 2019; Suga, et al., 2017)
TLCA 23.9 MDCKII-transfected NTCP, ASBT, OATP1B1, OATP1B3 (Balakrishnan, et al., 2006; Dong, et al., 2015; Suga, et al., 2019; Suga, et al., 2017)
TUDCA >2,000* MDCK-transfected; MDCKII-transfected NTCP, ASBT, OATP1A2, OATP1B1, OATP1B3, BSEP, MRP4 (Balakrishnan, et al., 2006; Ballatori, et al., 2005; Dong, et al., 2015; Hayashi, et al., 2005; Kramer, et al., 1999; Maeda, et al., 2006; Meier, et al., 1997; Rius, et al., 2006; Suga, et al., 2019; Suga, et al., 2017)
2. Other Endogenous Compounds
DHEAS 1.5 X. laevis oocytes-injected; Flp-In 293-transfected NTCP, OAT2, OAT3, OAT4, OAT7, OATP1A2, OATP1B1, OATP2B1, MRP1, MRP2, MRP4, BCRP (Ballatori, et al., 2005; Burckhardt, 2012; Cha, et al., 2001; Cha, et al., 2000; Cui, et al., 2001; Fang, et al., 2010; Grube, et al., 2007; Hagenbuch & Stieger, 2013; Kobayashi, et al., 2005; Kullak-Ublick, et al., 1998; Malinen, Kauttonen, et al., 2019; Miyajima, Kusuhara, Fujishima, Adachi, & Sugiyama, 2011; Pfeifer, Bridges, Ferslew, Hardwick, & Brouwer, 2013; Pizzagalli, et al., 2003; Yamada, et al., 2007; Zelcer, et al., 2003)
ES 320 X. laevis oocytes-injected; Flp-In 293-transfected NTCP, OAT2, OAT3, OAT4, OAT7, MATE1, MATE2-K, MRP1, BCRP (Ballatori, et al., 2005; Burckhardt, 2012; Burckhardt & Burckhardt, 2011; Cha, et al., 2000; Cui, et al., 2001; Grube, et al., 2007; Hagenbuch & Stieger, 2013; Hirano, Maeda, Shitara, & Sugiyama, 2006; Ho, et al., 2004; Imai, et al., 2003; Kobayashi, et al., 2005; Kullak-Ublick, et al., 2001; Lu, Gonzalez, & Klaassen, 2010; Malinen, et al., 2018; Miyazaki, et al., 2005; Noe, Portmann, Brun, & Funk, 2007; Nozawa, et al., 2004; Pizzagalli, et al., 2003; Qian, Song, Cui, Cole, & Deeley, 2001; Seward, et al., 2003; Terada & Inui, 2008; Tsuda, et al., 2007; Wang, et al., 2001; Yamaguchi, et al., 2010; Yamashita, et al., 2006; Zhou, Tanaka, Pan, Ma, & You, 2004)
PGE2 NA X. laevis oocytes-injected OCT1, OCT2, OAT1, OAT2, OAT3, OAT4, OATP2B1, MRP4 (Kimura, et al., 2002; Nishio, et al., 2000; Reid, et al., 2003; Seward, et al., 2003; Wang, et al., 2001)
PREGS 6.9 X. laevis oocytes-injected NTCP, OAT4, OATP2B1 (Fang, et al., 2010; Grube, Köck, Karner, et al., 2006; Kimura, et al., 2002)
3. Drugs
Atorvastatin NA HeLa-transfected NTCP, OATP1B1, OATP1B3, OATP2B1, P-gp, MRP2, BCRP (Choi, et al., 2011; Ellis, Hawksworth, & Weaver, 2013; Grube, Köck, Oswald, et al., 2006; Hochman, et al., 2004; Kameyama, Yamashita, Kobayashi, Hosokawa, & Chiba, 2005; Karlgren, et al., 2012; Keskitalo, et al., 2009; Lau, Huang, Frassetto, & Benet, 2007; Schwarz, 2012)
Digoxin NA X. laevis oocytes-injected OATP1B3, OATP4C1, P-gp, MDR3 (Kullak-Ublick, et al., 2001; Seward, et al., 2003; Smith, et al., 2000; Troutman & Thakker, 2003; Wang, et al., 2001)
Docetaxel NA HeLa-transfected OATP1A2, OATP1B1, OATP1B3, P-gp (de Graan, et al., 2012; Durmus, et al., 2014; Iusuflfet al., 2015; Lee, Leake, Kim, & Ho, 2017; Schwarz, 2012; Shirakawa, et al., 1999; Yamaguchi, et al., 2008)
Rosuvastatin NA HeLa-transfected NTCP, OAT3, OATP1A2, OATP1B1, OATP1B3, OATP2B1, P-gp, MRP2, MRP4, BCRP (Choi, et al., 2011; Dong, et al., 2015; Ellis, et al., 2013; Ho, et al., 2006; Keskitalo, et al., 2009; Kikuchi, et al., 2006; Kitamura, Maeda, Wang, & Sugiyama, 2008; Lu, et al., 2015; Pfeifer, et al., 2013; Schwarz, 2012; Windass, Lowes, Wang, & Brown, 2007)
Sulfasalazine NA HeLa-transfected OATP2B1, MRP2, BCRP (Schwarz, 2012; Urquhart, et al., 2008; Kusuhara, et al., 2012; Dahan & Amidon, 2009)
*

Reported Km values were higher than the maximum substrate concentration tested. CA, cholate; CDCA, chenodeoxycholate; DHEAS, dehydroepiandrosterone sulfate; ES, estrone sulfate; GCA, glycocholate; GCDCA, glycochenodeoxycholate; GDCA, glycodeoxycholate; GLCA, glycolithocholate; GUDCA, glycoursodeoxycholate; Km, substrate concentration at one-half of the maximum velocity; LCA; lithocholate; NA, data not available in the literature; PGE2, prostaglandin E2; PREGS, pregnenolone sulfate; TCA, taurocholate; TCDCA, taurochenodeoxycholate; TDCA, taurodeoxycholate; TLCA, taurolithocholate; TUDCA, tauroursodeoxycholate