Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFGXEB)

• DTT Name: Liver organic anion transporter 1 (SLCO1B1)
• Synonyms: Solute carrier organic anion transporter family member 1B1; Solute carrier family 21 member 6; Sodium-independent organic anion-transporting polypeptide 2; SLC21A6; OATPC; OATP2; OATP-C; OATP-2; Liver-specific organic anion transporter 1; LST1; LST-1
• Gene Name: SLCO1B1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Organo anion transporter
• UniProt ID: SO1B1_HUMAN
• TTD ID: T46814
• Sequence:
  MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKSSIIHIERRFE
  ISSSLVGFIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCFIMGIGGVLTALPHFFMGY
  YRYSKETNINSSENSTSTLSTCLINQILSLNRASPEIVGKGCLKESGSYMWIYVFMGNML
  RGIGETPIVPLGLSYIDDFAKEGHSSLYLGILNAIAMIGPIIGFTLGSLFSKMYVDIGYV
  DLSTIRITPTDSRWVGAWWLNFLVSGLFSIISSIPFFFLPQTPNKPQKERKASLSLHVLE
  TNDEKDQTANLTNQGKNITKNVTGFFQSFKSILTNPLYVMFVLLTLLQVSSYIGAFTYVF
  KYVEQQYGQPSSKANILLGVITIPIFASGMFLGGYIIKKFKLNTVGIAKFSCFTAVMSLS
  FYLLYFFILCENKSVAGLTMTYDGNNPVTSHRDVPLSYCNSDCNCDESQWEPVCGNNGIT
  YISPCLAGCKSSSGNKKPIVFYNCSCLEVTGLQNRNYSAHLGECPRDDACTRKFYFFVAI
  QVLNLFFSALGGTSHVMLIVKIVQPELKSLALGFHSMVIRALGGILAPIYFGALIDTTCI
  KWSTNNCGTRGSCRTYNSTSFSRVYLGLSSMLRVSSLVLYIILIYAMKKKYQEKDINASE
  NGSVMDEANLESLNKNKHFVPSAGADSETHC
• Function: Involved in the clearance of bile acids and organic anions from the liver. Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine.
• 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 DTT

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
[3H]estradiol-17beta-glucuronide	DM3KJ45	Discovery agent	N.A.	Investigative	[1]
[3H]estrone-3-sulphate	DMGPF0N	Discovery agent	N.A.	Investigative	[1]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP Info
• Gene Name: SLCO1B1

64 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acocantherin	DM7JT24	Atrial fibrillation	BC81.3	Approved	[2]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[3]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[4]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[5]
Bromfenac	DMKB79O	Pain	MG30-MG3Z	Approved	[6]
Caspofungin	DMGQIPT	Candidiasis	1F23	Approved	[7]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[7]
Cefditoren	DMSUVM1	Bacterial infection	1A00-1C4Z	Approved	[7]
Cefoperazone	DM53PV8	Bacterial infection	1A00-1C4Z	Approved	[7]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[8]
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[7]
Cilostazol	DMZMSCT	Intermittent claudication	BD40.00	Approved	[9]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[10]
Darunavir	DMN3GCH	Human immunodeficiency virus infection	1C62	Approved	[7]
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[10]
Dehydroepiandrosterone sulfate	DM4Q80H	N. A.	N. A.	Approved	[7]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[7]
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[8]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[11]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[12]
Entacapone	DMLBVKQ	Parkinson disease	8A00.0	Approved	[6]
Estrone sulfate	DMVBIZL	Atrophic vaginitis	GA30.2	Approved	[13]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[14]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[15]
FLUORESCEIN	DMQTFAO	Ocular disease	1F00.1Z	Approved	[6]
Fluvastatin	DM4MDJY	Arteriosclerosis	BD40	Approved	[16]
Gadobenate Dimeglumine	DM4VAOG	Schizophrenia	6A20	Approved	[17]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[10]
Hydroxyurea	DMOQVU9	Chronic myelogenous leukaemia	2A20.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Levothyroxine	DMHN027	Congenital hypothyroidism		Approved	[19]
Liothyronine	DM6IR3P	Congenital hypothyroidism		Approved	[19]
Lopinavir	DMITQS0	Human immunodeficiency virus infection	1C62	Approved	[7]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[20]
Mesalazine	DMOL5IU	Diverticulitis		Approved	[21]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[22]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[23]
Nafcillin	DMN9RPO	Arthritis	FA20	Approved	[7]
Nateglinide	DMLK2QH	Diabetic complication	5A2Y	Approved	[6]
Nilotinib	DM7HXWT	Chronic myelogenous leukaemia	2A20.0	Approved	[10]
Olmesartan medoxomil	DMWBHRY	High blood pressure	BA00	Approved	[24]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[25]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[7]
Pitavastatin	DMJH792	Hypercholesterolaemia	5C80.0	Approved	[26]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[27]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[27]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[28]
Repaglinide	DM5SXUV	Diabetic complication	5A2Y	Approved	[29]
Rifampin	DMA8J1G	Tuberculosis	1B10-1B1Z	Approved	[30]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[31]
Saquinavir	DMG814N	Human immunodeficiency virus infection	1C62	Approved	[7]
Simeprevir	DMLUA9D	Chronic HCV-1 infection	1E51.1	Approved	[32]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[33]
Sirolimus	DMGW1ID	Advanced cancer	2A00-2F9Z	Approved	[34]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[10]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[10]
Technetium (99MTC) mebrofenin	DMUEWM3	N. A.	N. A.	Approved	[29]
Temocapril	DM1A79H	N. A.	N. A.	Approved	[7]
Torasemide	DMXKJ6C	Congestive heart failure	BD10	Approved	[35]
Ursodeoxycholic acid	DMCUT21	Cholelithiasis	DC11	Approved	[36]
Valsartan	DMREUQ6	Chronic heart failure	BD1Z	Approved	[2]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[10]
Vemurafenib	DM62UG5	Melanoma	2C30	Approved	[10]
Primovist	DM37FKA	N. A.	N. A.	Phase 4	[7]

12 Clinical Trial Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Atrasentan	DMM74PK	Diabetic nephropathy	GB61.Z	Phase 3	[7]
Benzylpenicillin	DMS9503	Actinomycosis		Phase 3	[7]
Karenitecin	DMCRGY4	Lung cancer	2C25.0	Phase 3	[7]
BQ-123	DM0MO8I	Pulmonary arterial hypertension	BB01.0	Phase 2	[7]
Cholyl lysyl fluorescein	DMALN2M	N. A.	N. A.	Phase 2	[7]
Danoprevir	DM20MDU	Hepatitis C virus infection	1E51.1	Phase 2	[8]
Flavopiridol	DMKSUOI	Acute myeloid leukaemia	2A60	Phase 2	[7]
Gimatecan	DMSKMET	Breast cancer	2C60-2C65	Phase 2	[7]
LE-SN38	DMW50NF	Colorectal cancer	2B91.Z	Phase 2	[7]
YM-758	DMU79X2	Angina pectoris	BA40	Phase 2	[7]
Sodium taurocholate	DM3GO0J	Type-2 diabetes	5A11	Phase 1/2	[2]
Taurocholic Acid	DM2LZ8F	Type-2 diabetes	5A11	Phase 1/2	[19]

1 Discontinued Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TR-14035	DMWD39E	Multiple sclerosis	8A40	Discontinued in Phase 1	[37]

8 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
bilirubin	DMI0V4O	Discovery agent	N.A.	Investigative	[38]
bromsulphthalein	DM9W2ZV	N. A.	N. A.	Investigative	[39]
CCK-8	DMN0J4W	N. A.	N. A.	Investigative	[7]
DADLE	DMRM0OW	Discovery agent	N.A.	Investigative	[7]
Fluo-3	DMLO9FU	N. A.	N. A.	Investigative	[40]
glycocholic acid	DM0SXNM	Discovery agent	N.A.	Investigative	[7]
LTE4	DMCPB0Q	Discovery agent	N.A.	Investigative	[7]
[3H]estradiol-17beta-glucuronide	DM3KJ45	Discovery agent	N.A.	Investigative	[41]

References

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• [4] Meta-analysis of contribution of genetic polymorphisms in drug-metabolizing enzymes or transporters to axitinib pharmacokinetics. Eur J Clin Pharmacol. 2012 May;68(5):645-55.
• [5] Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007 Aug;35(8):1400-7.
• [6] Organic Anion Transporter 2-Mediated Hepatic Uptake Contributes to the Clearance of High-Permeability-Low-Molecular-Weight Acid and Zwitterion Drugs: Evaluation Using 25 Drugs. J Pharmacol Exp Ther. 2018 Nov;367(2):322-334.
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• [10] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [11] Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015 May;55(5):534-42.
• [12] The modified dipeptide, enalapril, an angiotensin-converting enzyme inhibitor, is transported by the rat liver organic anion transport protein. Hepatology. 1998 Nov;28(5):1341-6.
• [13] Role of transmembrane domain 10 for the function of organic anion transporting polypeptide 1B1. Protein Sci. 2009 Nov;18(11):2298-306.
• [14] Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
• [15] A LC-MS/MS method to quantify the novel cholesterol lowering drug ezetimibe in human serum, urine and feces in healthy subjects genotyped for SLCO1B1. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Jan 2;830(1):143-50.
• [16] SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clin Pharmacol Ther. 2006 Oct;80(4):356-66.
• [17] Liver Perfusion Modifies Gd-DTPA and Gd-BOPTA Hepatocyte Concentrations Through Transfer Clearances Across Sinusoidal Membranes. Eur J Drug Metab Pharmacokinet. 2017 Aug;42(4):657-667.
• [18] Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
• [19] Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem. 1999 Jun 11;274(24):17159-63.
• [20] A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8.
• [21] Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102.
• [22] Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
• [23] Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
• [24] OATP1B1, OATP1B3, and mrp2 are involved in hepatobiliary transport of olmesartan, a novel angiotensin II blocker. Drug Metab Dispos. 2006 May;34(5):862-9.
• [25] Interaction of human organic anion transporter polypeptides 1B1 and 1B3 with antineoplastic compounds. Eur J Med Chem. 2015 Mar 6;92:723-31.
• [26] Prediction of the in vivo OATP1B1-mediated drug-drug interaction potential of an investigational drug against a range of statins. Eur J Pharm Sci. 2012 Aug 30;47(1):244-55.
• [27] The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
• [28] Regorafenib is transported by the organic anion transporter 1B1 and the multidrug resistance protein 2. Biol Pharm Bull. 2015;38(4):582-6.
• [29] Disease-Associated Changes in Drug Transporters May Impact the Pharmacokinetics and/or Toxicity of Drugs: A White Paper From the International Transporter Consortium. Clin Pharmacol Ther. 2018 Nov;104(5):900-915.
• [30] Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8.
• [31] Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.
• [32] Drug-Drug Interactions with the NS3/4A Protease Inhibitor Simeprevir. Clin Pharmacokinet. 2016 Feb;55(2):197-208.
• [33] Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705.
• [34] Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2010 Jun;87(6):663-7.
• [35] Coleman J., Cox A. and Cowley N. (2011). Side Effects of Drugs Annual. Elsevier.
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• [37] Cellular entry of thyroid hormones by organic anion transporting polypeptides. Best Pract Res Clin Endocrinol Metab. 2007 Jun;21(2):209-21.
• [38] Role of organic anion-transporting polypeptides, OATP-A, OATP-C and OATP-8, in the human placenta-maternal liver tandem excretory pathway for foetal bilirubin. Biochem J. 2003 May 1;371(Pt 3):897-905.
• [39] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
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• [41] Identification, Ki determination and CoMFA analysis of nuclear receptor ligands as competitive inhibitors of OATP1B1-mediated estradiol-17beta-glucuronide transport. Pharmacol Res. 2009 Jul;60(1):50-6.