Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNEN8QK)

• DOT Name: Solute carrier organic anion transporter family member 1B1 (SLCO1B1)
• Synonyms: SLCO1B1; Liver-specific organic anion transporter 1; LST-1; OATP-C; Organic anion transporter SLC21A6; Sodium-independent organic anion-transporting polypeptide 2; OATP-2; Solute carrier family 21 member 6
• Gene Name: SLCO1B1
• Related Disease: Rotor syndrome
• UniProt ID: SO1B1_HUMAN
• PDB ID: 8HNB; 8HNC; 8HND; 8HNH; 8K6L; 8PHW
• Pfam ID: PF07648 ; PF03137
• Sequence:
  MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKSSIIHIERRFE
  ISSSLVGFIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCFIMGIGGVLTALPHFFMGY
  YRYSKETNINSSENSTSTLSTCLINQILSLNRASPEIVGKGCLKESGSYMWIYVFMGNML
  RGIGETPIVPLGLSYIDDFAKEGHSSLYLGILNAIAMIGPIIGFTLGSLFSKMYVDIGYV
  DLSTIRITPTDSRWVGAWWLNFLVSGLFSIISSIPFFFLPQTPNKPQKERKASLSLHVLE
  TNDEKDQTANLTNQGKNITKNVTGFFQSFKSILTNPLYVMFVLLTLLQVSSYIGAFTYVF
  KYVEQQYGQPSSKANILLGVITIPIFASGMFLGGYIIKKFKLNTVGIAKFSCFTAVMSLS
  FYLLYFFILCENKSVAGLTMTYDGNNPVTSHRDVPLSYCNSDCNCDESQWEPVCGNNGIT
  YISPCLAGCKSSSGNKKPIVFYNCSCLEVTGLQNRNYSAHLGECPRDDACTRKFYFFVAI
  QVLNLFFSALGGTSHVMLIVKIVQPELKSLALGFHSMVIRALGGILAPIYFGALIDTTCI
  KWSTNNCGTRGSCRTYNSTSFSRVYLGLSSMLRVSSLVLYIILIYAMKKKYQEKDINASE
  NGSVMDEANLESLNKNKHFVPSAGADSETHC
• Function: Mediates the Na(+)-independent uptake of organic anions. Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop. Involved in the clearance of endogenous and exogenous substrates from the liver. Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition. May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs. May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate. May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver. Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment. Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions.
• Tissue Specificity: Highly expressed in liver, at the basolateral membranes of centrilobular hepatocytes . Expressed in liver (at protein level) . Expressed in fetal liver . Not detected in heart, brain, placenta, lung, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocyte . In testis, primarily localized to the basal membrane of Sertoli cells and weakly expressed in Leydig cells and within the tubules .
• KEGG Pathway: Bile secretion (hsa04976)
• Reactome Pathway:
  Heme degradation (R-HSA-189483)
  Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR) (R-HSA-5619110)
  Transport of organic anions (R-HSA-879518)
  Atorvastatin ADME (R-HSA-9754706)
  Recycling of bile acids and salts (R-HSA-159418)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rotor syndrome	DISNBRRT	Supportive	Autosomal recessive	[1]

This DOT Affected the Regulation of Drug Effects of 21 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) affects the abundance of Arsenic.	[27]
Quercetin	DM3NC4M	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the uptake of Quercetin.	[28]
Hydroxyurea	DMOQVU9	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the uptake of Hydroxyurea.	[33]
Ursodeoxycholic acid	DMCUT21	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the uptake of Ursodeoxycholic acid.	[34]
Deoxycholic acid	DM3GYAL	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the uptake of Deoxycholic acid.	[34]
Glutathione	DMAHMT9	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the import of Glutathione.	[35]
Cholic acid	DM7OKQV	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the uptake of Cholic acid.	[34]
Fexofenadine	DM17ONX	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the uptake of Fexofenadine.	[36]
Enalapril	DMNFUZR	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) affects the abundance of Enalapril.	[37]
Repaglinide	DM5SXUV	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) affects the metabolism of Repaglinide.	[38]
Enalaprilat	DMFYAM1	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) affects the abundance of Enalaprilat.	[37]
Atorvastatin	DMF28YC	Phase 3 Trial	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) decreases the transport of Atorvastatin.	[39]
MK-8245	DMG6KXB	Phase 2	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the uptake of MK-8245.	[40]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) affects the uptake of 3R14S-OCHRATOXIN A.	[41]
	DM9CEI5		Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the uptake of .	[34]
Hydroxydimethylarsine Oxide	DMPS2B1	Investigative	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the abundance of Hydroxydimethylarsine Oxide.	[27]
[3H]estrone-3-sulphate	DMGPF0N	Investigative	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) decreases the transport of [3H]estrone-3-sulphate.	[43]
Asacolitin	DM3WVPJ	Investigative	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the uptake of Asacolitin.	[44]
[3H]estradiol-17beta-glucuronide	DM3KJ45	Investigative	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) decreases the transport of [3H]estradiol-17beta-glucuronide.	[43]
Glycocholic acid	DM0SXNM	Investigative	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the abundance of Glycocholic acid.	[45]
Taurochenodeoxycholic acid	DMEL9UT	Investigative	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the transport of Taurochenodeoxycholic acid.	[46]

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the response to substance of Methotrexate.	[29]
Aspirin	DM672AH	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the Acute lymphocytic leukaemia ADR of Aspirin.	[30]
Irinotecan	DMP6SC2	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the Neutropenias ADR of Irinotecan.	[31]
Simvastatin	DM30SGU	Approved	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the response to substance of Simvastatin.	[32]
Microcystin-LR	DMTMLRN	Investigative	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) increases the response to substance of Microcystin-LR.	[42]
Talinolol	DMRTD16	Investigative	Solute carrier organic anion transporter family member 1B1 (SLCO1B1) affects the response to substance of Talinolol.	[47]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[2]

27 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan affects the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[6]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[7]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[8]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[9]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[10]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[11]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[12]
Lovastatin	DM9OZWQ	Approved	Lovastatin decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[13]
Atazanavir	DMSYRBX	Approved	Atazanavir decreases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[10]
Trospium chloride	DM32XZT	Approved	Trospium chloride decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[14]
Rifamycin	DMEH3O7	Approved	Rifamycin decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[13]
Fusidic acid	DMWVCF3	Approved	Fusidic acid decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[15]
TAK-875	DMIM5AP	Phase 3	TAK-875 decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[17]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[19]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[20]
PKI166	DMSQ794	Discontinued in Phase 2	PKI166 decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[23]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[24]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[25]
Bilirubin	DMI0V4O	Investigative	Bilirubin increases the expression of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[26]
Kaempferol	DMHEMUB	Investigative	Kaempferol decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[20]
biochanin A	DM0HPWY	Investigative	biochanin A decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[20]
LICOAGROCHACONE A	DMWY0TN	Investigative	LICOAGROCHACONE A decreases the activity of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[20]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine affects the localization of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[16]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the degradation of Solute carrier organic anion transporter family member 1B1 (SLCO1B1).	[22]

References

• [1] Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest. 2012 Feb;122(2):519-28. doi: 10.1172/JCI59526. Epub 2012 Jan 9.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
• [6] Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine. Clin Pharmacol Ther. 2006 Nov;80(5):440-456.
• [7] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [8] Identification of pregnane X receptor binding sites in the regulatory regions of genes involved in bile acid homeostasis. J Mol Biol. 2005 Feb 18;346(2):505-19. doi: 10.1016/j.jmb.2004.12.003. Epub 2005 Jan 5.
• [9] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [10] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
• [11] Chenodeoxycholic acid significantly impacts the expression of miRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes. Life Sci. 2016 Jul 1;156:47-56.
• [12] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [13] Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos. 2005 Apr;33(4):537-46.
• [14] Expression of drug transporters and drug metabolizing enzymes in the bladder urothelium in man and affinity of the bladder spasmolytic trospium chloride to transporters likely involved in its pharmacokinetics. Mol Pharm. 2015 Jan 5;12(1):171-8.
• [15] Inhibition of Hepatobiliary Transport Activity by the Antibacterial Agent Fusidic Acid: Insights into Factors Contributing to Conjugated Hyperbilirubinemia/Cholestasis. Chem Res Toxicol. 2016 Oct 17;29(10):1778-1788. doi: 10.1021/acs.chemrestox.6b00262. Epub 2016 Oct 4.
• [16] Downregulation of Organic Anion Transporting Polypeptide (OATP) 1B1 Transport Function by Lysosomotropic Drug Chloroquine: Implication in OATP-Mediated Drug-Drug Interactions. Mol Pharm. 2016 Mar 7;13(3):839-51. doi: 10.1021/acs.molpharmaceut.5b00763. Epub 2016 Feb 1.
• [17] Mechanistic investigations of the liver toxicity of the free fatty acid receptor 1 agonist fasiglifam (TAK875) and its primary metabolites. J Biochem Mol Toxicol. 2019 Aug;33(8):e22345. doi: 10.1002/jbt.22345. Epub 2019 May 8.
• [18] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [19] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [20] Drug interaction study of flavonoids toward OATP1B1 and their 3D structure activity relationship analysis for predicting hepatoprotective effects. Toxicology. 2020 May 15;437:152445. doi: 10.1016/j.tox.2020.152445. Epub 2020 Apr 4.
• [21] Hepatic transport of PKI166, an epidermal growth factor receptor kinase inhibitor of the pyrrolo-pyrimidine class, and its main metabolite, ACU154. Drug Metab Dispos. 2004 Nov;32(11):1272-8. doi: 10.1124/dmd.104.000497. Epub 2004 Jul 27.
• [22] Amino-terminal region of human organic anion transporting polypeptide 1B1 dictates transporter stability and substrate interaction. Toxicol Appl Pharmacol. 2019 Sep 1;378:114642. doi: 10.1016/j.taap.2019.114642. Epub 2019 Jun 27.
• [23] Inhibition of SLC drug transporter activities by environmental bisphenols. Toxicol In Vitro. 2017 Apr;40:34-44. doi: 10.1016/j.tiv.2016.12.009. Epub 2016 Dec 15.
• [24] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [25] Comparison of long-term versus short-term effects of okadaic acid on the apoptotic status of human HepaRG cells. Chem Biol Interact. 2020 Feb 1;317:108937. doi: 10.1016/j.cbi.2020.108937. Epub 2020 Jan 8.
• [26] Interleukin 1beta inhibits CAR-induced expression of hepatic genes involved in drug and bilirubin clearance. Hepatology. 2004 Oct;40(4):951-60.
• [27] SLCO1B1 variants and urine arsenic metabolites in the Strong Heart Family Study. Toxicol Sci. 2013 Nov;136(1):19-25. doi: 10.1093/toxsci/kft181. Epub 2013 Aug 22.
• [28] Organic anion transporting polypeptides and organic cation transporter 1 contribute to the cellular uptake of the flavonoid quercetin. Naunyn Schmiedebergs Arch Pharmacol. 2014 Sep;387(9):883-91. doi: 10.1007/s00210-014-1000-6. Epub 2014 Jun 20.
• [29] SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients. Toxicol Sci. 2014 Nov;142(1):196-209. doi: 10.1093/toxsci/kfu162. Epub 2014 Aug 14.
• [30] Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol. 2009 Dec 10;27(35):5972-8.
• [31] Severe toxicities after irinotecan-based chemotherapy in a patient with lung cancer: a homozygote for the SLCO1B1*15 allele. Ther Drug Monit. 2007 Oct;29(5):666-8. doi: 10.1097/FTD.0b013e3181357364.
• [32] SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med. 2008 Aug 21;359(8):789-99.
• [33] Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
• [34] Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J Lipid Res. 2006 Jun;47(6):1196-202.
• [35] Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells. J Biomed Sci. 2006 Jul;13(4):525-33. doi: 10.1007/s11373-006-9071-0. Epub 2006 Feb 15.
• [36] Involvement of multiple efflux transporters in hepatic disposition of fexofenadine. Mol Pharmacol. 2008 May;73(5):1474-83.
• [37] Effect of organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphism on the single- and multiple-dose pharmacokinetics of enalapril in healthy Chinese adult men. Clin Ther. 2011 May;33(5):655-63. doi: 10.1016/j.clinthera.2011.04.018.
• [38] Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics. Clin Pharmacol Ther. 2005 Jun;77(6):468-78. doi: 10.1016/j.clpt.2005.01.018.
• [39] Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells. Pharmacogenet Genomics. 2005 Jul;15(7):513-22.
• [40] Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia. J Med Chem. 2011 Jul 28;54(14):5082-96.
• [41] Ochratoxin A transport by the human breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), and organic anion-transporting polypeptides 1A2, 1B1 and 2B1. Toxicol Appl Pharmacol. 2017 Aug 15;329:18-25. doi: 10.1016/j.taap.2017.05.022. Epub 2017 May 19.
• [42] Involvement of mitogen-activated protein kinase signaling pathways in microcystin-LR-induced apoptosis after its selective uptake mediated by OATP1B1 and OATP1B3. Toxicol Sci. 2007 Jun;97(2):407-16. doi: 10.1093/toxsci/kfm054. Epub 2007 Mar 16.
• [43] Functional analysis of a mutation in the SLCO1B1 gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy. Pharmacogenomics J. 2009 Jun;9(3):185-93. doi: 10.1038/tpj.2009.3. Epub 2009 Feb 24.
• [44] Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102.
• [45] Enteric microbiome metabolites correlate with response to simvastatin treatment. PLoS One. 2011;6(10):e25482. doi: 10.1371/journal.pone.0025482. Epub 2011 Oct 13.
• [46] Human OATP1B1 (SLCO1B1) transports sulfated bile acids and bile salts with particular efficiency. Toxicol In Vitro. 2018 Oct;52:189-194. doi: 10.1016/j.tiv.2018.06.018. Epub 2018 Jun 19.
• [47] Simvastatin does not influence the intestinal P-glycoprotein and MPR2, and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1, ABCC2 and SLCO1B1 polymorphisms. Br J Clin Pharmacol. 2006 Apr;61(4):440-50. doi: 10.1111/j.1365-2125.2006.02599.x.