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
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
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 Adenocarcinoma 2D40 Approved [4]
Clonidine DM6RZ9Q Attention deficit hyperactivity disorder 6A05.Z Approved [5]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [6]
Dofetilide DMPN1TW Sinus rhythm disorder BC9Y Approved [7]
Dopamine DMPGUCF Acromegaly 5A60.0 Approved [8]
Ergotidine DM78IME Osteoarthritis FA00-FA05 Approved [9]
Famotidine DMRL3AB Gastric ulcer DA60 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 Colorectal carcinoma Approved [14]
Norepinephrine DMOUC09 Alopecia ED70 Approved [8]
Oxaliplatin DMQNWRD Adenocarcinoma 2D40 Approved [15]
Pramipexole DMNMW9R Parkinson disease 8A00.0 Approved [16]
Propranolol DM79NTF Angina pectoris BA40 Approved [5]
Quinine DMSWYF5 Malaria 1F40-1F45 Approved [17]
Ranitidine DM0GUSX Gastric ulcer DA60 Approved [10]
Varenicline DMMUOLJ Drug dependence Approved [18]
------------------------------------------------------------------------------------
⏷ Show the Full List of 22 Approved Drug(s)
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 N. A. N. A. Preclinical [21]
------------------------------------------------------------------------------------
3 Investigative Drug(s) Transported by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CHOLINE DM5D9YK Insomnia 7A00-7A0Z 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.