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

General Information of Drug (ID: DM07HYA)

• Drug Name: 5,6-dinitroacenaphthoquinone Drug Info
• Synonyms: 5,6-dinitroacenaphthoquinone; 5,6-dinitroacenaphthylene-1,2-dione; AC1MQHVL; 5,6-dinitroacenaphthenequinone; CHEMBL235289; SCHEMBL2699746; BDBM22854; MolPort-003-895-771; 1,2-Dione-Based Compound, 11; AKOS024343013; MCULE-5132922926; 27471-02-9; 5,6-dinitro-1,2-dihydroacenaphthylenedione

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 3477013
  TTD Drug ID: DM07HYA

Molecule-Related Drug Atlas

Drug(s) Targeting Acetylcholinesterase (AChE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tacrine	DM51FY6	Alzheimer disease	8A20	Approved	[2]
Donepezil	DMIYG7Z	Advanced cancer	2A00-2F9Z	Approved	[3]
Malathion	DMXZ84M	Pediculus capitis infestation	1G00.0	Approved	[4]
Galantamine	DMEO794	Alzheimer disease	8A20	Approved	[5]
Huperzine A	DMMAWLU	Alzheimer disease	8A20	Approved	[6]
Neostigmine	DM6T2J3	Myasthenia gravis	8C6Y	Approved	[7]
YM443	DMNZCI1	Functional dyspepsia	DD90.3	Approved	[8]
Ambenonium	DMOP0BL	Myasthenia gravis	8C6Y	Approved	[9]
Demecarium bromide	DMAYEU1	Open-angle glaucoma	9C61	Approved	[10]
Isoflurophate	DMBSK7X	Glaucoma/ocular hypertension	9C61	Approved	[11]

Drug(s) Targeting Liver carboxylesterase (CES1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[12]
PACTIMIBE	DM0NZDT	Arteriosclerosis	BD40	Phase 2/3	[13]
K-604	DMQVN6P	Arteriosclerosis	BD40	Phase 2	[14]
Eldacimibe	DML7WP0	Hyperlipidaemia	5C80	Phase 2	[15]
GR148672X	DM7W6YN	Acute lymphoblastic leukaemia	2A85	Clinical trial	[16]
Avasimibe	DMFG4OM	Peripheral vascular disease	BD4Z	Discontinued in Phase 3	[17]
E-5324	DM562BM	Hyperlipidaemia	5C80	Discontinued in Phase 2	[18]
RP-64477	DMTQ3BS	Hyperlipidaemia	5C80	Discontinued in Phase 2	[19]
CI-976	DMBO28J	Hyperlipidaemia	5C80	Discontinued in Phase 2	[20]
CL-283796	DM7LIDT	Hyperlipidaemia	5C80	Discontinued in Phase 2	[21]

Drug(s) Targeting Cholinesterase (BCHE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hexafluronium bromide	DMFY307	Spasm	MB47.3	Approved	[22]
MEPTAZINOL	DMPSB8F	Pain	MG30-MG3Z	Approved	[23]
Eptastigmine	DMTV7ZM	Cognitive impairment	6D71	Phase 3	[24]
(-)-Phenserine	DMNCY1I	Alzheimer disease	8A20	Phase 3	[25]
Plasma derived human butyrylcholinesterase	DMF3IBC	Neurotoxicity	NE61	Phase 1	[26]
Protexia	DME1Y9W	Alzheimer disease	8A20	Phase 1	[27]
JES-9501	DMYR3IE	Alzheimer disease	8A20	Phase 1	[28]
Tetra-hydro-isoquinoline derivative 3	DMCZA45	N. A.	N. A.	Patented	[29]
Tetra-hydro-isoquinoline derivative 1	DML86IO	N. A.	N. A.	Patented	[29]
Tetra-hydro-isoquinoline derivative 2	DM5CKVF	N. A.	N. A.	Patented	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Acetylcholinesterase (AChE)	TT1RS9F	ACES_HUMAN	Inhibitor	[1]
Cholinesterase (BCHE)	TTEB0GD	CHLE_HUMAN	Inhibitor	[1]
Liver carboxylesterase (CES1)	TTMF541	EST1_HUMAN	Inhibitor	[1]

References

• [1] Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1. J Med Chem. 2007 Nov 15;50(23):5727-34.
• [2] Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action. Int J Clin Pract Suppl. 2002 Jun;(127):6-19.
• [3] 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. (Target id: 2465).
• [4] Acetylcholinesterase activity in Corbicula fluminea Mull., as a biomarker of organophosphate pesticide pollution in Pinacanauan River, Philippines. Environ Monit Assess. 2010 Jun;165(1-4):331-40.
• [5] [From symptomatic to disease modifying therapy Recent developments in the pharmacotherapy of Alzheimer's disease]. Fortschr Neurol Psychiatr. 2009 Jun;77(6):326-33.
• [6] Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia-ischemia. Brain Res. 2002 Sep 13;949(1-2):162-70.
• [7] Screening of acetylcholinesterase inhibitors by CE after enzymatic reaction at capillary inlet. J Sep Sci. 2009 May;32(10):1748-56.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [9] Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens. Neuropsychopharmacology. 2008 Aug;33(9):2158-66.
• [10] The effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase levels in normal dogs. Vet Ophthalmol. 2003 Mar;6(1):23-5.
• [11] Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Chem Biol. 2003 Jun;10(6):491-502.
• [12] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [13] Novel indoline-based acyl-CoA:cholesterol acyltransferase inhibitor with antiperoxidative activity: improvement of physicochemical properties and b... J Med Chem. 2008 Aug 14;51(15):4823-33.
• [14] A selective ACAT-1 inhibitor, K-604, suppresses fatty streak lesions in fat-fed hamsters without affecting plasma cholesterol levels. Atherosclerosis. 2007 Apr;191(2):290-7.
• [15] Prospects for drug therapy for hyperlipoproteinaemia. Diabete Metab. 1995 Apr;21(2):139-46.
• [16] 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. (Target id: 2592).
• [17] New advances in lipid-modifying therapies for reducing cardiovascular risk. Cardiology. 2002;97(2):59-66.
• [18] Effect of the acyl-CoA:cholesterol acyltransferase inhibitor, E5324, on experimental atherosclerosis in rabbits. Atherosclerosis. 1994 Jun;107(2):187-201.
• [19] RP 64477: a potent inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase with low systemic bioavailability. Biochem Pharmacol. 1996 Feb 23;51(4):413-21.
• [20] Acyl-coenzyme A:cholesterol-acyltransferase (ACAT) inhibitors modulate monocyte adhesion to aortic endothelial cells. Atherosclerosis. 1995 Jan 6;112(1):7-17.
• [21] ACAT inhibitors CL 283,546 and CL 283,796 reduce LDL cholesterol without affecting cholesterol absorption in African green monkeys. J Lipid Res. 1995 Jun;36(6):1199-210.
• [22] Synergistic effect of acidosis and succinylcholine-induced hyperkalemia in spinal cord transected rats. Acta Anaesthesiol Scand. 1984 Feb;28(1):87-90.
• [23] Bis-(-)-nor-meptazinols as novel nanomolar cholinesterase inhibitors with high inhibitory potency on amyloid-beta aggregation. J Med Chem. 2008 Apr 10;51(7):2027-36.
• [24] Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine. J Med Chem. 2006 Apr 6;49(7):2174-85.
• [25] Long-acting anticholinesterases for myasthenia gravis: synthesis and activities of quaternary phenylcarbamates of neostigmine, pyridostigmine and physostigmine. Bioorg Med Chem. 2010 Jul 1;18(13):4687-93.
• [26] Acetylcholinesterase-Fc Fusion Protein (AChE-Fc): A Novel Potential Organophosphate Bioscavenger with Extended Plasma Half-Life. Bioconjug Chem. 2015 Aug 19;26(8):1753-8.
• [27] In vitro and in vivo characterization of recombinant human butyrylcholinesterase (Protexia) as a potential nerve agent bioscavenger. Chem Biol Interact. 2005 Dec 15;157-158:363-5.
• [28] Dehydroevodiamine attenuates beta-amyloid peptide-induced amnesia in mice. Eur J Pharmacol. 2001 Feb 16;413(2-3):221-5.
• [29] A patent review of butyrylcholinesterase inhibitors and reactivators 2010-2017.Expert Opin Ther Pat. 2018 Jun;28(6):455-465.