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

General Information of Drug (ID: DM8DT7U)

• Drug Name: ABT-089 Drug Info
• Synonyms: Pozanicline; A 94224; ABT 089; Pozanicline (USAN); (R)-2-Methyl-3-(2-pyrrolidinylmethoxy)pyridine; 2-Methyl-3-(2-pyrrolidinylmethoxy)pyridine; 2-Methyl-3-(2S-pyrrolidinylmethoxy)pyridine; 2-methyl-3-[[(2R)-pyrrolidin-2-yl]methoxy]pyridine; 2-methyl-3-[[(2S)-pyrrolidin-2-yl]methoxy]pyridine

Indication

Disease Entry	ICD 11	Status	REF
Anxiety disorder	6B00-6B0Z	Discontinued in Phase 2	[1]
Attention deficit hyperactivity disorder	6A05.Z	Discontinued in Phase 2	[1]
Dementia	6D80-6D86	Discontinued in Phase 2	[1]
Schizophrenia	6A20	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 178052
  CAS Number: CAS 161417-03-4
  TTD Drug ID: DM8DT7U

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
Varenicline	DMMUOLJ	Drug dependence		Approved	[5]
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]

Drug(s) Affected By Neuronal acetylcholine receptor subunit beta-2 (CHRNB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[15]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Atropine	DMEN6X7	Organophosphate poisoning	NE6Z	Approved	[17]
Galantamine	DMEO794	Alzheimer disease	8A20	Approved	[17]
Rivastigmine	DMG629M	Alzheimer disease	8A20	Approved	[17]
Scopolamine	DMOM8AL	Addictive disorder	6C50-6C5Z	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[19]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[20]
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[3]

Drug(s) Affected By Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[21]
Selenium	DM25CGV	N. A.	N. A.	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Atropine	DMEN6X7	Organophosphate poisoning	NE6Z	Approved	[17]
Galantamine	DMEO794	Alzheimer disease	8A20	Approved	[17]
Rivastigmine	DMG629M	Alzheimer disease	8A20	Approved	[17]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[23]
Scopolamine	DMOM8AL	Addictive disorder	6C50-6C5Z	Approved	[17]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[24]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[25]

Drug(s) Affected By Neuronal acetylcholine receptor subunit alpha-7 (CHRNA7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[26]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Acetylcholine	DMDF79Z	Cataract	9B10	Approved	[4]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[27]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[28]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[29]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[30]
Carbachol	DMX9K8F	Glaucoma/ocular hypertension	9C61	Approved	[31]
Cotinine	DMCEZ1B	Insecticide	N.A.	Approved	[4]
Urethane	DM7NSI0	N. A.	N. A.	Phase 4	[32]

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	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4)	OT1H0ZXC	ACHA4_HUMAN	Protein Interaction/Cellular Processes	[3]
Neuronal acetylcholine receptor subunit alpha-7 (CHRNA7)	OTBUSUTE	ACHA7_HUMAN	Drug Response	[4]
Neuronal acetylcholine receptor subunit beta-2 (CHRNB2)	OTNAT2M5	ACHB2_HUMAN	Protein Interaction/Cellular Processes	[3]

References

• [1] Emerging drugs for attention-deficit/hyperactivity disorder. Expert Opin Emerg Drugs. 2007 Sep;12(3):423-34.
• [2] Selectivity of ABT-089 for alpha4beta2* and alpha6beta2* nicotinic acetylcholine receptors in brain.Biochem Pharmacol.2009 Oct 1;78(7):795-802.
• [3] ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties. J Pharmacol Exp Ther. 1997 Oct;283(1):235-46.
• [4] Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant. Eur J Pharmacol. 1999 Feb 5;366(2-3):301-8. doi: 10.1016/s0014-2999(98)00909-1.
• [5] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [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] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [16] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [17] Cholinergic drugs potentiate human nicotinic alpha4beta2 acetylcholine receptors by a competitive mechanism. Eur J Pharmacol. 2005 Feb 21;509(2-3):97-108. doi: 10.1016/j.ejphar.2004.12.037.
• [18] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [19] Repetitive nicotine exposure leads to a more malignant and metastasis-prone phenotype of SCLC: a molecular insight into the importance of quitting smoking during treatment. Toxicol Sci. 2010 Aug;116(2):467-76. doi: 10.1093/toxsci/kfq138. Epub 2010 May 10.
• [20] Molecular modelling of the interactions of carbamazepine and a nicotinic receptor involved in the autosomal dominant nocturnal frontal lobe epilepsy. Br J Pharmacol. 2002 Jul;136(6):883-95. doi: 10.1038/sj.bjp.0704786.
• [21] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [22] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [23] Rosiglitazone inhibits alpha4 nicotinic acetylcholine receptor expression in human lung carcinoma cells through peroxisome proliferator-activated receptor gamma-independent signals. Mol Cancer Ther. 2009 Jan;8(1):110-8. doi: 10.1158/1535-7163.MCT-08-0719.
• [24] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [25] The C terminus of the human nicotinic alpha4beta2 receptor forms a binding site required for potentiation by an estrogenic steroid. J Neurosci. 2001 Sep 1;21(17):6561-8. doi: 10.1523/JNEUROSCI.21-17-06561.2001.
• [26] Effects of cannabidiol on the function of 7-nicotinic acetylcholine receptors. Eur J Pharmacol. 2013 Nov 15;720(1-3):310-9. doi: 10.1016/j.ejphar.2013.10.011. Epub 2013 Oct 18.
• [27] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [28] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [29] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [30] Nicotine-induced Ca2+ signaling and down-regulation of nicotinic acetylcholine receptor subunit expression in the CEM human leukemic T-cell line. Life Sci. 2003 Mar 28;72(18-19):2155-8. doi: 10.1016/s0024-3205(03)00077-8.
• [31] Counteracting desensitization of human 7-nicotinic acetylcholine receptors with bispyridinium compounds as an approach against organophosphorus poisoning. Toxicol Lett. 2018 Sep 1;293:149-156. doi: 10.1016/j.toxlet.2017.12.005. Epub 2017 Dec 14.
• [32] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.