Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTDL3UZ)

• DTT Name: Organic anion transporter B (SLCO2B1)
• Synonyms: Solute carrier organic anion transporter family member 2B1; Solute carrier family 21 member 9; SLC21A9; Organic anion transporter polypeptide-related protein 2; OATPRP2; OATPB; OATP2B1; OATP-RP2; OATP-B; KIAA0880
• Gene Name: SLCO2B1
• DTT Type: Literature-reported target; [1]
• UniProt ID: SO2B1_HUMAN
• TTD ID: T34064
• Sequence:
  MGPRIGPAGEVPQVPDKETKATMGTENTPGGKASPDPQDVRPSVFHNIKLFVLCHSLLQL
  AQLMISGYLKSSISTVEKRFGLSSQTSGLLASFNEVGNTALIVFVSYFGSRVHRPRMIGY
  GAILVALAGLLMTLPHFISEPYRYDNTSPEDMPQDFKASLCLPTTSAPASAPSNGNCSSY
  TETQHLSVVGIMFVAQTLLGVGGVPIQPFGISYIDDFAHNSNSPLYLGILFAVTMMGPGL
  AFGLGSLMLRLYVDINQMPEGGISLTIKDPRWVGAWWLGFLIAAGAVALAAIPYFFFPKE
  MPKEKRELQFRRKVLAVTDSPARKGKDSPSKQSPGESTKKQDGLVQIAPNLTVIQFIKVF
  PRVLLQTLRHPIFLLVVLSQVCLSSMAAGMAIFLPKFLERQFSITASYANLLIGCLSFPS
  VIVGIVVGGVLVKRLHLGPVGCGALCLLGMLLCLFFSLPLFFIGCSSHQIAGITHQTSAH
  PGLELSPSCMEACSCPLDGFNPVCDPSTRVEYITPCHAGCSSWVVQDALDNSQVFYTNCS
  CVVEGNPVLAGSCDSTCSHLVVPFLLLVSLGSALACLTHTPSFMLILRGVKKEDKTLAVG
  IQFMFLRILAWMPSPVIHGSAIDTTCVHWALSCGRRAVCRYYNNDLLRNRFIGLQFFFKT
  GSVICFALVLAVLRQQDKEARTKESRSSPAVEQQLLVSGPGKKPEDSRV
• Function: Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
• Reactome Pathway:
  Transport of organic anions (R-HSA-879518)
  Aspirin ADME (R-HSA-9749641)
  Atorvastatin ADME (R-HSA-9754706)
  Heme degradation (R-HSA-189483)

Molecular Interaction Atlas (MIA) of This DTT

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
[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 2B1 (SLCO2B1) DTP Info
• Gene Name: SLCO2B1

29 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Abiraterone acetate	DMANBZI	Prostate cancer	2C82.0	Approved	[2]
Aliskiren	DM1BV7W	Hypertension	BA00-BA04	Approved	[3]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[4]
BOL-303259-X	DM2EXC5	Open-angle glaucoma	9C61	Approved	[5]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[6]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[7]
Dehydroepiandrosterone sulfate	DM4Q80H	N. A.	N. A.	Approved	[8]
Digoxin	DMQCTIH	Arrhythmia	BC9Z	Approved	[9]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[10]
Eltrombopag	DMOGFIX	Thrombocytopenia	3B64	Approved	[11]
Estrone sulfate	DMVBIZL	Atrophic vaginitis	GA30.2	Approved	[12]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[13]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[14]
Fluvastatin	DM4MDJY	Arteriosclerosis	BD40	Approved	[12]
Glibenclamide	DM8JXPZ	Diabetic complication	5A2Y	Approved	[15]
L-Glutamic Acid	DM4PUDW	Schizophrenia	6A20	Approved	[16]
Latanoprost	DMI5OXG	Ocular hypertension	9C61.01	Approved	[5]
lifitegrast	DM4WVC5	Dry eye disease	9E1Z	Approved	[17]
Mesalazine	DMOL5IU	Diverticulitis		Approved	[18]
Montelukast	DMD157S	Allergic asthma	CA23.0	Approved	[19]
Pemetrexed	DMMX2E6	Central nervous system lymphoma	2B33.5	Approved	[20]
Pitavastatin	DMJH792	Hypercholesterolaemia	5C80.0	Approved	[21]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[22]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[23]
Ritonavir	DMU764S	Human immunodeficiency virus infection	1C62	Approved	[24]
Rocuronium	DMY9BMK	Muscle spasm	MB47.3	Approved	[9]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[25]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[26]
Telmisartan	DMS3GX2	Hypertension	BA00-BA04	Approved	[27]

4 Clinical Trial Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alilusem	DM9R2SD	Diuretic vasodilator	BA00	Phase 3	[28]
Benzylpenicillin	DMS9503	Actinomycosis		Phase 3	[10]
Sodium taurocholate	DM3GO0J	Type-2 diabetes	5A11	Phase 1/2	[23]
Taurocholic Acid	DM2LZ8F	Type-2 diabetes	5A11	Phase 1/2	[23]

1 Preclinical Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Scutellarin	DMJT1E5	N. A.	N. A.	Preclinical	[29]

2 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
bromsulphthalein	DM9W2ZV	N. A.	N. A.	Investigative	[30]
talinolol	DMRTD16	Discovery agent	N.A.	Investigative	[31]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1224).
• [2] The impact of statin use on the efficacy of abiraterone acetate in patients with castration-resistant prostate cancer. Prostate. 2017 May;77(13):1303-1311.
• [3] Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren. Br J Clin Pharmacol. 2011 May;71(5):718-26.
• [4] Human platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin. Drug Metab Dispos. 2009 May;37(5):1129-37.
• [5] The prostaglandin transporter OATP2A1 is expressed in human ocular tissues and transports the antiglaucoma prostanoid latanoprost. Invest Ophthalmol Vis Sci. 2010 May;51(5):2504-11.
• [6] 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.
• [7] pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
• [8] Expression of OATP family members in hormone-related cancers: potential markers of progression. PLoS One. 2011;6(5):e20372.
• [9] Drug Interactions in Infectious Diseases.
• [10] Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60.
• [11] Pharmacokinetics and hepatic uptake of eltrombopag, a novel platelet-increasing agent. Drug Metab Dispos. 2011 Jun;39(6):1088-96.
• [12] Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos. 2007 Aug;35(8):1308-14.
• [13] 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.
• [14] The effects of the SLCO2B1 c.1457C>T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans. Pharmacogenet Genomics. 2011 Feb;21(2):84-93.
• [15] Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos. 2005 Apr;33(4):518-23.
• [16] The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.60.1.20)
• [17] Clinical Pharmacology and Biopharmaceutics review(s)
• [18] Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102.
• [19] Effects of polymorphisms of the SLCO2B1 transporter gene on the pharmacokinetics of montelukast in humans. J Clin Pharmacol. 2013 Nov;53(11):1186-93.
• [20] Substrate- and pH-specific antifolate transport mediated by organic anion-transporting polypeptide 2B1 (OATP2B1-SLCO2B1). Mol Pharmacol. 2012 Feb;81(2):134-42.
• [21] Intestinal absorption of HMG-CoA reductase inhibitor pitavastatin mediated by organic anion transporting polypeptide and P-glycoprotein/multidrug resistance 1. Drug Metab Pharmacokinet. 2011;26(2):171-9.
• [22] Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36.
• [23] Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
• [24] pH dependence of organic anion-transporting polypeptide 2B1 in Caco-2 cells: potential role in antiretroviral drug oral bioavailability and drug-drug interactions. J Pharmacol Exp Ther. 2010 Sep 1;334(3):1009-22.
• [25] Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.
• [26] Small-Dosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1 and ABCG2), and Interaction (Atorvastatin and Grapefruit Juice) Profiles of 5 Probes for OATP2B1 and BCRP. J Pharm Sci. 2017 Sep;106(9):2688-2694.
• [27] Establishment of a set of double transfectants coexpressing organic anion transporting polypeptide 1B3 and hepatic efflux transporters for the characterization of the hepatobiliary transport of telmisartan acylglucuronide. Drug Metab Dispos. 2008 Apr;36(4):796-805.
• [28] Characterization of the uptake mechanism for a novel loop diuretic, M17055, in Caco-2 cells: involvement of organic anion transporting polypeptide (OATP)-B. Pharm Res. 2007 Jan;24(1):90-8.
• [29] Mechanistic studies on the absorption and disposition of scutellarin in humans: selective OATP2B1-mediated hepatic uptake is a likely key determinant for its unique pharmacokinetic characteristics. Drug Metab Dispos. 2012 Oct;40(10):2009-20.
• [30] Organic anion-transporting polypeptide (OATP) 2B1 contributes to the cellular uptake of theaflavin. Drug Metab Pharmacokinet. 2017 Apr;32(2):145-150.
• [31] Species difference in the effect of grapefruit juice on intestinal absorption of talinolol between human and rat. J Pharmacol Exp Ther. 2010 Jan;332(1):181-9.