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

General Information of Drug (ID: DMEN5KA)

• Drug Name: GTS-21 Drug Info
• Synonyms: Gts-21; DMXBA; Gts 21; DMXB-Anabaseine; GTS-21 (dihydrochloride); DMXB-A; (E)-3-((2,4-Dimethoxyphenyl)methylene)-3,4,5,6-tetrahydro-2,3'-bipyridine dihydrochloride; 2,3'-Bipyridine, 3-((2,4-dimethoxyphenyl)methylene)-3,4,5,6-tetrahydro-, dihydrochloride, (E)-; DMBX-anabaseine; DMBX-A; AC1O5PJQ; SCHEMBL2561893; SCHEMBL12274790; HY-14564A; CS-5486; SB16826; BC654014; AN-16572; GTS-21, > LS-173500; 3-(2,4-Dimethoxybenzylidene)anabaseine dihydrochloride

Indication

Disease Entry	ICD 11	Status	REF
Parkinson disease	8A00.0	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 5310985
  CAS Number: CAS 148372-04-7
  TTD Drug ID: DMEN5KA
  INTEDE Drug ID: DR0792

Molecule-Related Drug Atlas

Drug(s) Targeting Neuronal acetylcholine receptor alpha-7 (CHRNA7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ziprasidone	DMM58JY	Bipolar disorder	6A60	Approved	[5]
ALCURONIUM	DM2U4XQ	Anaesthesia	9A78.6	Approved	[6]
AMG 386	DMQJXL4	Breast cancer	2C60-2C65	Phase 3	[7]
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[8]
EVP-6124	DMLQO7F	Alzheimer disease	8A20	Phase 3	[9]
JNJ-39393406	DMUOEKM	Depression	6A70-6A7Z	Phase 2	[10]
ABT-126	DM2OS51	Alzheimer disease	8A20	Phase 2	[11]
TC-6987	DMNFP21	Asthma	CA23	Phase 2	[12]
AQW-051	DMD2RFO	Alzheimer disease	8A20	Phase 2	[13]
MEM-3454	DMPNDYU	Schizophrenia	6A20	Phase 2	[5]

Drug(s) Metabolized By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[14]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[21]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[23]

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	[24]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[25]
Acetylcholine	DMDF79Z	Cataract	9B10	Approved	[4]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[26]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[27]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[28]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[29]
Carbachol	DMX9K8F	Glaucoma/ocular hypertension	9C61	Approved	[30]
Cotinine	DMCEZ1B	Insecticide	N.A.	Approved	[4]
Urethane	DM7NSI0	N. A.	N. A.	Phase 4	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Neuronal acetylcholine receptor alpha-7 (CHRNA7)	TTLA931	ACHA7_HUMAN	Agonist	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Neuronal acetylcholine receptor subunit alpha-7 (CHRNA7)	OTBUSUTE	ACHA7_HUMAN	Drug Response	[4]

References

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• [2] The brain alpha7 nicotinic receptor may be an important therapeutic target for the treatment of Alzheimer's disease: studies with DMXBA (GTS-21). Behav Brain Res. 2000 Aug;113(1-2):169-81.
• [3] Metabolism and disposition of GTS-21, a novel drug for Alzheimer's disease. Xenobiotica. 1999 Jul;29(7):747-62.
• [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] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [6] Pharmacological characteristics and binding modes of caracurine V analogues and related compounds at the neuronal alpha7 nicotinic acetylcholine re... J Med Chem. 2007 Sep 20;50(19):4616-29.
• [7] Clinical pipeline report, company report or official report of Roche (2009).
• [8] 3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation. Bioorg Med Chem Lett. 2005 Nov 15;15(22):4889-97.
• [9] Normalizing effects of EVP-6124, an alpha-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia. J Psychiatr Pract. 2014 Jan;20(1):12-24.
• [10] Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. Neuropharmacology. 2013 Jan;64:197-204.
• [11] A phase 2 randomized, controlled trial of the alpha7 agonist ABT-126 in mild-to-moderate Alzheimer's dementia. Alzheimer's & Dementia: Translational Research & Clinical Interventions Volume 1, Issue 1, June 2015, Pages 81-90.
• [12] ClinicalTrials.gov (NCT01293669) Glycemic Control, Safety and Tolerability of TC-6987 Monotherapy in Type 2 Diabetes Mellitus. U.S. National Institutes of Health.
• [13] AQW051, a novel and selective nicotinic acetylcholine receptor alpha7 partial agonist, reduces l-Dopa-induced dyskinesias and extends the duration of l-Dopa effects in parkinsonian monkeys. Parkinsonism Relat Disord. 2014 Nov;20(11):1119-23.
• [14] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [15] Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
• [16] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [17] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [18] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [19] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [22] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [23] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
• [24] 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.
• [25] 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.
• [26] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [27] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.