Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTTYH7A)

• DTT Name: Organic anion transporter 1
• Synonyms: Solute carrier family 22 member 6; Kidney-specific transport protein; Novel kidney transcript; PAH transporter; Renal organic anion transporter 1; hOAT1; hPAHT; hROAT1; mNKT; mROAT1; SLC22A6
• Gene Name: SLC22A6
• BioChemical Class: Single Protein
• UniProt ID: S22A6_HUMAN
• TTD ID: TE0109
• Sequence:
  MAFNDLLQQVGGVGRFQQIQVTLVVLPLLLMASHNTLQNFTAAIPTHHCRPPADANLSKN
  GGLEVWLPRDRQGQPESCLRFTSPQWGLPFLNGTEANGTGATEPCTDGWIYDNSTFPSTI
  VTEWDLVCSHRALRQLAQSLYMVGVLLGAMVFGYLADRLGRRKVLILNYLQTAVSGTCAA
  FAPNFPIYCAFRLLSGMALAGISLNCMTLNVEWMPIHTRACVGTLIGYVYSLGQFLLAGV
  AYAVPHWRHLQLLVSAPFFAFFIYSWFFIESARWHSSSGRLDLTLRALQRVARINGKREE
  GAKLSMEVLRASLQKELTMGKGQASAMELLRCPTLRHLFLCLSMLWFATSFAYYGLVMDL
  QGFGVSIYLIQVIFGAVDLPAKLVGFLVINSLGRRPAQMAALLLAGICILLNGVIPQDQS
  IVRTSLAVLGKGCLAASFNCIFLYTGELYPTMIRQTGMGMGSTMARVGSIVSPLVSMTAE
  LYPSMPLFIYGAVPVAASAVTVLLPETLGQPLPDTVQDLESRWAPTQKEAGIYPRKGKQT
  RQQQEHQKYMVPLQASAQEKNGL
• Function: Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP), ochratoxin (OTA).

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Organic anion transporter 1 (SLC22A6) DTP Info
• Gene Name: SLC22A6

23 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aciclovir	DMYLOVR	Genital herpes	1A94	Approved	[1]
Adefovir	DMM278X	N. A.	N. A.	Approved	[2]
Alprostadil	DMWH7NQ	Aorta coarctation		Approved	[3]
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[4]
Cefaclor	DMJXDGC	Bacterial infection	1A00-1C4Z	Approved	[5]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[6]
Ceftizoxime	DM3VOGS	Acute gonococcal cervicitis		Approved	[5]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[7]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[8]
Famotidine	DMRL3AB	Gastric ulcer	DA60	Approved	[9]
FLUORESCEIN	DMQTFAO	Ocular disease	1F00.1Z	Approved	[10]
Furosemide	DMMQ8ZG	Congestive heart failure	BD10	Approved	[11]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[1]
MCI-186	DM8ZHP1	Amyotrophic lateral sclerosis	8B60.0	Approved	[12]
Meropenem	DM62UHC	Bacterial infection	1A00-1C4Z	Approved	[13]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[14]
Mycophenolic acid	DMRBMAU	Crohn disease	DD70	Approved	[15]
Olmesartan medoxomil	DMWBHRY	High blood pressure	BA00	Approved	[16]
Oseltamivir	DMGO72P	Influenza	1E30-1E32	Approved	[5]
Tenofovir	DM1IS6U	Chronic hepatitis B virus infection		Approved	[17]
Trifluridine	DMG2YBD	Herpetic keratitis	1F00.10	Approved	[18]
Zalcitabine	DMH7MUV	Human immunodeficiency virus infection	1C62	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[1]

2 Clinical Trial Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dimesna	DMU4T9Y	Diabetic nephropathy	GB61.Z	Phase 3	[20]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[8]

5 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3R14S-OCHRATOXIN A	DM2KEW6	Discovery agent	N.A.	Investigative	[21]
6-Carboxyfluorescein	DMWTMDH	N. A.	N. A.	Investigative	[22]
AMINOHIPPURIC ACID	DMUN54G	Discovery agent	N.A.	Investigative	[23]
GLUTARATE	DMPUFDS	Discovery agent	N.A.	Investigative	[22]
uric acid	DMA1MKT	Discovery agent	N.A.	Investigative	[24]

References

• [1] Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
• [2] Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1. J Am Soc Nephrol. 2000 Mar;11(3):383-93.
• [3] Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3. Prostaglandins Other Lipid Mediat. 2016 Jan;122:10-7.
• [4] The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies. Drug Metab Dispos. 2002 Jan;30(1):13-9.
• [5] FDA Drug Development and Drug Interactions
• [6] Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res. 2004 Jan;21(1):61-7.
• [7] Renal transport of adefovir, cidofovir, and tenofovir by SLC22A family members (hOAT1, hOAT3, and hOCT2). Pharm Res. 2007 Apr;24(4):811-5.
• [8] Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
• [9] Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Eur J Pharmacol. 2004 Oct 25;503(1-3):25-30.
• [10] Apical expression or expression in a non polarized cell of hOAT1 inverses regulation by epidermal growth factor (EGF) as compared to basolateral hOAT1. Cell Physiol Biochem. 2004;14(3):177-86.
• [11] Interactions of human organic anion transporters with diuretics. J Pharmacol Exp Ther. 2004 Mar;308(3):1021-9.
• [12] Human organic anion transporters 1 (hOAT1/SLC22A6) and 3 (hOAT3/SLC22A8) transport edaravone (MCI-186; 3-methyl-1-phenyl-2-pyrazolin-5-one) and its sulfate conjugate. Drug Metab Dispos. 2007 Aug;35(8):1429-34.
• [13] Characterization of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, and meropenem as substrates of human renal transporters. Drug Metab Pharmacokinet. 2007 Feb 25;22(1):41-7.
• [14] Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug Metab Pharmacokinet. 2010;25(2):163-9.
• [15] Interaction and transport characteristics of mycophenolic acid and its glucuronide via human organic anion transporters hOAT1 and hOAT3. Biochem Pharmacol. 2007 Jun 30;74(1):161-8.
• [16] Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug Metab Dispos. 2007 Dec;35(12):2166-76.
• [17] Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs. Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):641-8.
• [18] Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9.
• [19] Interaction of zalcitabine with human organic anion transporter 1. Pharmazie. 2006 May;61(5):491-2.
• [20] In vitro and in vivo assessment of renal drug transporters in the disposition of mesna and dimesna. J Clin Pharmacol. 2012 Apr;52(4):530-42.
• [21] Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35.
• [22] Fluorescence-based assay for the interaction of small molecules with the human renal organic anion transporter 1. Anal Biochem. 2000 Jul 15;283(1):49-55.
• [23] Interactions of human organic anion transporter 1 (hOAT1) with substances associated with forensic toxicology. Leg Med (Tokyo). 2011 Jul;13(4):180-5.
• [24] Involvement of uric acid transporters in alteration of serum uric acid level by angiotensin II receptor blockers. Pharm Res. 2008 Mar;25(3):639-46.