Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMVUKEW)

• Drug Name: N-methylpyridinium Drug Info
• Synonyms: 1-Methyl-Pyridinium; 1-Methylpyridin-1-ium; 1-Methylpyridinium; N-Methylpyridinium; Pyridinium, 1-methyl-

Indication

Disease Entry	ICD 11	Status	REF
Colon cancer	2B90.Z	Preclinical	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 13597
  ChEBI ID: ChEBI:15761
  TTD Drug ID: DMVUKEW
  VARIDT Drug ID: DR00337

Molecule-Related Drug Atlas

Drug(s) Transported By Organic cation transporter 2 (SLC22A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[6]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[7]
Oxaliplatin	DMQNWRD	Colorectal cancer	2B91.Z	Approved	[8]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[9]
Dopamine	DMPGUCF	Parkinson disease	8A00.0	Approved	[10]
Propranolol	DM79NTF	Migraine	8A80	Approved	[11]
Ergotidine	DM78IME	Respiratory allergy	4A80	Approved	[12]
Metformin	DM89QE1	Type-2 diabetes	5A11	Approved	[13]
Clonidine	DM6RZ9Q	Hypertension	BA00-BA04	Approved	[11]
Ranitidine	DM0GUSX	Peptic ulcer	DA61	Approved	[14]

Drug(s) Transported By Multidrug and toxin extrusion protein 1 (SLC47A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aciclovir	DMYLOVR	Virus infection	1A24-1D9Z	Approved	[4]
Metformin	DM89QE1	Type-2 diabetes	5A11	Approved	[15]
Ganciclovir	DM1MBYQ	Virus infection	1A24-1D9Z	Approved	[4]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[4]
Chloroquine	DMSI5CB	Malaria	1F40-1F45	Approved	[16]
Procainamide	DMNMXR8	Ventricular arrhythmias	BC71	Approved	[4]
Topotecan	DMP6G8T	Ovarian cancer	2C73	Approved	[4]
Cephalexin	DMD5JU8	Bacterial infection	1A00-1C4Z	Approved	[17]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[18]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[19]

Drug(s) Transported By Organic cation transporter 3 (SLC22A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Propranolol	DM79NTF	Migraine	8A80	Approved	[11]
Ergotidine	DM78IME	Respiratory allergy	4A80	Approved	[10]
Metformin	DM89QE1	Type-2 diabetes	5A11	Approved	[20]
Clonidine	DM6RZ9Q	Hypertension	BA00-BA04	Approved	[11]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[21]
Epinephrine	DM3KJBC	Allergy	4A80-4A85	Approved	[10]
Norepinephrine	DMOUC09	Sepsis	1G40-1G41	Approved	[10]
Amphetamine	DMSZQAK	Attention deficit hyperactivity disorder	6A05.Z	Approved	[22]
Acetylcholine	DMDF79Z	Cataract	9B10	Approved	[23]
Sodium chloride	DMM3950	Skin burns	ME65.0	Approved	[24]

Drug(s) Transported By Organic cation transporter 1 (SLC22A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[6]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[25]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Oxaliplatin	DMQNWRD	Colorectal cancer	2B91.Z	Approved	[27]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[28]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[29]
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[30]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[31]
Dopamine	DMPGUCF	Parkinson disease	8A00.0	Approved	[32]
Propranolol	DM79NTF	Migraine	8A80	Approved	[11]

Drug(s) Transported By Multidrug and toxin extrusion protein 2 (SLC47A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aciclovir	DMYLOVR	Virus infection	1A24-1D9Z	Approved	[4]
Metformin	DM89QE1	Type-2 diabetes	5A11	Approved	[4]
Ganciclovir	DM1MBYQ	Virus infection	1A24-1D9Z	Approved	[4]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[4]
Procainamide	DMNMXR8	Ventricular arrhythmias	BC71	Approved	[4]
Topotecan	DMP6G8T	Ovarian cancer	2C73	Approved	[4]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[18]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[19]
Estrone sulfate	DMVBIZL	Menopausal and postmenopausal disorder	GA30	Approved	[4]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[4]

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[2]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[3]
Multidrug and toxin extrusion protein 2 (SLC47A2)	DT3TX4H	S47A2_HUMAN	Substrate	[4]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[4]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[5]

References

• [1] Wikipedia: Methylpyridinium
• [2] Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58.
• [3] Interaction of oral antidiabetic drugs with hepatic uptake transporters: focus on organic anion transporting polypeptides and organic cation transporter 1. Diabetes. 2008 Jun;57(6):1463-9.
• [4] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
• [5] Functional characterization of the human organic cation transporter 2 variant p.270Ala>Ser. Drug Metab Dispos. 2009 Jun;37(6):1312-8.
• [6] Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
• [7] Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005 Dec;167(6):1477-84.
• [8] 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.
• [9] Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81.
• [10] Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
• [11] 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.
• [12] 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.
• [13] Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86.
• [14] 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.
• [15] Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Am J Physiol Renal Physiol. 2010 Apr;298(4):F997-F1005.
• [16] Molecular mechanism of renal tubular secretion of the antimalarial drug chloroquine. Antimicrob Agents Chemother. 2011 Jul;55(7):3091-8.
• [17] Reduced renal clearance of a zwitterionic substrate cephalexin in MATE1-deficient mice. J Pharmacol Exp Ther. 2010 Aug;334(2):651-6.
• [18] Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
• [19] FDA Drug Development and Drug Interactions
• [20] Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology. 2009 Oct;50(4):1227-40.
• [21] Multiple SLC and ABC Transporters Contribute to the Placental Transfer of Entecavir. Drug Metab Dispos. 2017 Mar;45(3):269-278.
• [22] Interaction of organic cation transporter 3 (SLC22A3) and amphetamine. J Neurochem. 2010 Jul;114(1):142-9.
• [23] Organic cation transporters: physiology, toxicology and special focus on ethidium as a novel substrate. Curr Drug Metab. 2009 Jul;10(6):617-31.
• [24] Organic cation transporter 3 (Slc22a3) is implicated in salt-intake regulation. J Neurosci. 2004 Mar 17;24(11):2846-51.
• [25] Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family). J Pharmacol Exp Ther. 2006 Nov;319(2):879-86.
• [26] Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008 Apr;49(4):639-42.
• [27] Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
• [28] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [29] Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
• [30] Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma
• [31] Comparison of type I and type II organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5.
• [32] Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences. Drug Metab Pharmacokinet. 2008;23(4):243-53.