Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0XOJN)

• DTT Name: Organic cation transporter 2
• Synonyms: Solute carrier family 22 member 2; hOCT2; SLC22A2
• Gene Name: SLC22A2
• BioChemical Class: Single Protein
• UniProt ID: S22A2_HUMAN
• TTD ID: TE0107
• Sequence:
  MPTTVDDVLEHGGEFHFFQKQMFFLLALLSATFAPIYVGIVFLGFTPDHRCRSPGVAELS
  LRCGWSPAEELNYTVPGPGPAGEASPRQCRRYEVDWNQSTFDCVDPLASLDTNRSRLPLG
  PCRDGWVYETPGSSIVTEFNLVCANSWMLDLFQSSVNVGFFIGSMSIGYIADRFGRKLCL
  LTTVLINAAAGVLMAISPTYTWMLIFRLIQGLVSKAGWLIGYILITEFVGRRYRRTVGIF
  YQVAYTVGLLVLAGVAYALPHWRWLQFTVSLPNFFFLLYYWCIPESPRWLISQNKNAEAM
  RIIKHIAKKNGKSLPASLQRLRLEEETGKKLNPSFLDLVRTPQIRKHTMILMYNWFTSSV
  LYQGLIMHMGLAGDNIYLDFFYSALVEFPAAFMIILTIDRIGRRYPWAASNMVAGAACLA
  SVFIPGDLQWLKIIISCLGRMGITMAYEIVCLVNAELYPTFIRNLGVHICSSMCDIGGII
  TPFLVYRLTNIWLELPLMVFGVLGLVAGGLVLLLPETKGKALPETIEEAENMQRPRKNKE
  KMIYLQVQKLDIPLN
• Function: Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamine, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin.

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Organic cation transporter 2 (SLC22A2) DTP Info
• Gene Name: SLC22A2

22 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amantadine	DMS3YE9	Influenza A virus infection	1E30	Approved	[1]
Amiloride	DMRTSGP	Congestive heart failure	BD10	Approved	[2]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[3]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Clonidine	DM6RZ9Q	Hypertension	BA00-BA04	Approved	[5]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[6]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[7]
Dopamine	DMPGUCF	Parkinson disease	8A00.0	Approved	[8]
Ergotidine	DM78IME	Respiratory allergy	4A80	Approved	[9]
Famotidine	DMRL3AB	Peptic ulcer	DA61	Approved	[10]
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[11]
Lamivudine	DMI347A	Chronic HBV infection	1E51.0Z	Approved	[12]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[13]
Memantine	DMD9WSC	Alzheimer disease	8A20	Approved	[1]
Metformin	DM89QE1	Type-2 diabetes	5A11	Approved	[14]
Norepinephrine	DMOUC09	Sepsis	1G40-1G41	Approved	[8]
Oxaliplatin	DMQNWRD	Colorectal cancer	2B91.Z	Approved	[15]
Pramipexole	DMNMW9R	Parkinson disease	8A00.0	Approved	[16]
Propranolol	DM79NTF	Migraine	8A80	Approved	[5]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[17]
Ranitidine	DM0GUSX	Peptic ulcer	DA61	Approved	[10]
Varenicline	DMMUOLJ	Smoking dependence	6C4A.2	Approved	[18]

2 Clinical Trial Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ym155	DM5Q1W4	Breast cancer	2C60-2C65	Phase 2	[19]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[20]

1 Preclinical Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
N-methylpyridinium	DMVUKEW	Colon cancer	2B90.Z	Preclinical	[21]

3 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Choline	DM5D9YK	Discovery agent	N.A.	Investigative	[22]
Serotonin	DMOFCRY	Discovery agent	N.A.	Investigative	[8]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[23]

References

• [1] Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52.
• [2] Characterization of regulatory mechanisms and states of human organic cation transporter 2. Am J Physiol Cell Physiol. 2006 Jun;290(6):C1521-31.
• [3] Elevated systemic elimination of cimetidine in rats with acute biliary obstruction: the role of renal organic cation transporter OCT2. Drug Metab Pharmacokinet. 2010;25(4):328-34.
• [4] Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005 Dec;167(6):1477-84.
• [5] Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
• [6] Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
• [7] FDA Drug Development and Drug Interactions
• [8] Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
• [9] The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua. Mol Reprod Dev. 2007 Oct;74(10):1303-11.
• [10] A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005 Oct;315(1):337-45.
• [11] Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine. Br J Clin Pharmacol. 2010 May;69(5):498-507.
• [12] Genetic variants of organic cation transporter 1 (OCT1) and OCT2 significantly reduce lamivudine uptake. Biopharm Drug Dispos. 2012 Apr;33(3):170-8.
• [13] Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
• [14] Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86.
• [15] Relevance of copper transporter 1 and organic cation transporters 1-3 for oxaliplatin uptake and drug resistance in colorectal cancer cells. Metallomics. 2018 Mar 1;10(3):414-425.
• [16] Uptake of pramipexole by human organic cation transporters. Mol Pharm. 2010 Aug 2;7(4):1342-7.
• [17] Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81.
• [18] Effect of human renal cationic transporter inhibition on the pharmacokinetics of varenicline, a new therapy for smoking cessation: an in vitro-in vivo study. Clin Pharmacol Ther. 2008 Apr;83(4):567-76.
• [19] Characterization of human organic cation transporter 1 (OCT1/SLC22A1)- and OCT2 (SLC22A2)-mediated transport of 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)- 4,9-dihydro-1H-naphtho[2,3-d]imidazolium bromide (YM155 monobromide), a novel small molecule survivin suppressant. Drug Metab Dispos. 2010 Jan;38(1):1-4.
• [20] Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
• [21] Functional characterization of the human organic cation transporter 2 variant p.270Ala>Ser. Drug Metab Dispos. 2009 Jun;37(6):1312-8.
• [22] Ventricular choline transport: a role for organic cation transporter 2 expressed in choroid plexus. J Biol Chem. 2001 Nov 9;276(45):41611-9.
• [23] Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochim Biophys Acta. 1999 Mar 4;1417(2):224-31.