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

General Information of Drug (ID: DMMUOLJ)

• Drug Name: Varenicline Drug Info
• Synonyms: CP 526555; Champix (TN); Chantix (TN); Varenicline (INN); 7,8,9,10-Tetrahydro-6,10-methano-6H-pyrazino(2,3-h)(3)benzazepine; 7,8,9,10-tetrahydro-6h-6,10-methanoazepino[4,5-g]quinoxaline

Indication

Disease Entry	ICD 11	Status	REF
Drug dependence		Approved	[1]
Smoking dependence	6C4A.2	Approved	[2]

• Cross-matching ID:
  PubChem CID: 170361
  CAS Number: CAS 249296-44-4
  TTD Drug ID: DMMUOLJ
  VARIDT Drug ID: DR00237
  ACDINA Drug ID: D00722

Molecule-Related Drug Atlas

Drug(s) Targeting Neuronal acetylcholine receptor alpha-4/beta-2 (CHRNA4/B2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metocurine Iodide	DMZJYBW	Anaesthesia	9A78.6	Approved	[6]
AZD-1446	DM7B1AR	Alzheimer disease	8A20	Phase 2	[7]
TC-6499-12	DMWPI2U	Irritable bowel syndrome	DD91.0	Phase 2	[8]
Sofinicline	DM157U0	Attention deficit hyperactivity disorder	6A05.Z	Phase 2	[9]
CP-601927	DMKJFDM	Gastrointestinal disease	DE2Z	Phase 2	[10]
TC-2216	DM4W92J	Mood disorder	6A60-6E23	Phase 1	[11]
SUVN 911	DMZP671	Major depressive disorder	6A70.3	Phase 1	[12]
Dianicline	DMX2SHT	Tobacco dependence	6C4A.2	Discontinued in Phase 3	[13]
TC-2696	DMP1A4S	Pain	MG30-MG3Z	Discontinued in Phase 2	[14]
Ispronicline	DMKY2UE	Alzheimer disease	8A20	Discontinued in Phase 2	[15]

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	[16]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[17]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[18]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[19]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[20]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[21]
Ergotidine	DM78IME	Osteoarthritis	FA00-FA05	Approved	[22]
Metformin	DM89QE1	Colorectal carcinoma		Approved	[23]
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[21]
Ranitidine	DM0GUSX	Gastric ulcer	DA60	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	[16]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[25]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[27]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[28]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[29]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[30]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[31]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[32]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Neuronal acetylcholine receptor alpha-4/beta-2 (CHRNA4/B2)	TTL1ATN	ACHA4_HUMAN; ACHB2_HUMAN	Modulator	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[4]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[5]

References

• [1] Varenicline FDA Label
• [2] 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. (Ligand id: 5459).
• [3] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [4] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [5] 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.
• [6] NMR study of general anesthetic interaction with nAChR beta2 subunit.Biophys J.2008 Mar 1;94(5):1681-8.
• [7] A randomized, double-blind, placebo-controlled crossover study of 4 2* nicotinic acetylcholine receptor agonist AZD1446 (TC-6683) in adults with attention-deficit/hyperactivity disorder.Psychopharmacology (Berl). 2014 Mar;231(6):1251-65.
• [8] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [9] Sofinicline: a novel nicotinic acetylcholine receptor agonist in the treatment of attention-deficit/hyperactivity disorder. Expert Opin Investig Drugs. 2014 Aug;23(8):1157-63.
• [10] Toxicity study in juvenile rats with the alpha4beta2 nicotinic acetylcholine receptor partial agonist CP-601,927. Birth Defects Res B Dev Reprod Toxicol. 2011 Aug;92(4):323-32.
• [11] TC-5214 (S-(+)-mecamylamine): a neuronal nicotinic receptor modulator with antidepressant activity.CNS Neurosci Ther.2008 Winter;14(4):266-77.
• [12] Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine alpha42 Receptor Antagonist for the Treatment of Depression. J Med Chem. 2020 Mar 26;63(6):2833-2853.
• [13] Dianicline, a novel 42 nicotinic acetylcholine receptor partial agonist, for smoking cessation: a randomized placebo-controlled clinical trial.Nicotine Tob Res.2011 Jan;13(1):1-6.
• [14] alpha4beta2 Nicotinic receptors play a role in the nAChR-mediated decline in L-dopa-induced dyskinesias in parkinsonian rats. Neuropharmacology. 2013 Aug;71:191-203.
• [15] Ispronicline: a novel alpha4beta2 nicotinic acetylcholine receptor-selective agonist with cognition-enhancing and neuroprotective properties. J Mol Neurosci. 2006;30(1-2):19-20.
• [16] Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
• [17] Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005 Dec;167(6):1477-84.
• [18] 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.
• [19] Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81.
• [20] Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
• [21] 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.
• [22] 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.
• [23] Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86.
• [24] 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.
• [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.