Understand the potential drug-bile salt interaction liabilities of your compound by using our BSEP, MRP2, MRP3 or MRP4 inhibition assays.
BSEP and MRP inhibition is in our portfolio of in vitro transporter services. Cyprotex deliver consistent, high quality BSEP and MRP inhibition data.
Proactive evaluation and understanding of BSEP inhibition is recommended in drug discovery and development to aid internal decision making on DILI risk.
5Kenna JG et al., (2018) Clin Pharmacol Ther 104(5); 916-932
|Test System||Sf9 insect cell-derived or mammalian (HEK293) cell-derived inside-out membrane vesicles overexpressing a single transporter (BSEP, MRP2, MRP3 or MRP4) incubated in the presence of ATP and AMP (absence of ATP).|
|Probe Substrate||[3H]-Taurocholic acid (BSEP)
[3H]-Estradiol 17β-glucuronide (MRPs)
|Test Article Concentrations||6 concentrations plus 0 μM (triplicate wells) (final test compound concentrations dependent on customer requirements)|
|Time Point||Dependent on transporter|
|Analysis Method||Radiochemical detection using scintillation counting|
Written report available on request
|Transporter||Substrate||Inhibitor||Mean IC50 ± Standard Deviation (µM)|
|BSEP||Taurocholic acid||Ketoconazole||8.78 ± 1.25|
|MRP2||Estradiol 17β-glucuronide||MK-571||22.6 ± 6.38|
|MRP3||Estradiol 17β-glucuronide||Terfenadine||33.5 ± 6.77|
|MK-571||56.8 ± 7.23|
|Fidaxomicin||1.06 ± 0.117|
|MRP4||Estradiol 17β-glucuronide||MK-571||0.555 ± 0.238|
|Indomethacin||3.79 ± 0.342|
|Ibuprofen||42.0 ± 23.7|
1 Wang L et al., (2002) The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II. J Clin Invest 110(7); 965-972
2 Dawson PA, Lan T, and Rao A. (2009) Bile acid transporters. Journal of Lipid Research 50(12); 2340-2357
3 Stieger B (2010) Role of the bile salt export pump, BSEP, in acquired forms of cholestasis. Drug Metab Rev 42(3); 437-445
4 The European Medicines Agency (EMA) Guideline on the Investigation of Drug Interactions (Adopted 2012)
5Kenna JG et al., (2018) Can bile salt export pump inhibition testing in drug discovery and development reduce liver injury risk? An International Transporter Consortium perspective. Clin Pharmacol Ther 104(5); 916-932
6 Zamek-Gliszczynski MJ et al., (2018) Transporters in drug development: 2018 ITC recommendations for transporters of emerging clinical importance. Clin Pharmacol Ther 104(5); 890-899
7 Morgan RE et al., (2013) A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development, Toxicol Sci 136; 216-241
Learn more about permeability and drug transporters in our popular Everything you need to know about ADME guide.