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

General Information of Drug (ID: DMNCY1I)

• Drug Name: (-)-Phenserine Drug Info
• Synonyms: (-)-Phenserine; CHEMBL54727; SCHEMBL5464366; BDBM10622; (3aS)-1,3a,8-trimethyl-1H,2H,3H,3aH,8H,8aH-pyrrolo[2,3-b]indol-5-yl N-phenylcarbamate

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 192706
  CAS Number: CAS 101246-66-6
  TTD Drug ID: DMNCY1I

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	[4]
Donepezil	DMIYG7Z	Advanced cancer	2A00-2F9Z	Approved	[5]
Malathion	DMXZ84M	Pediculus capitis infestation	1G00.0	Approved	[6]
Galantamine	DMEO794	Alzheimer disease	8A20	Approved	[7]
Huperzine A	DMMAWLU	Alzheimer disease	8A20	Approved	[8]
Neostigmine	DM6T2J3	Myasthenia gravis	8C6Y	Approved	[9]
YM443	DMNZCI1	Functional dyspepsia	DD90.3	Approved	[10]
Ambenonium	DMOP0BL	Myasthenia gravis	8C6Y	Approved	[11]
Demecarium bromide	DMAYEU1	Open-angle glaucoma	9C61	Approved	[12]
Isoflurophate	DMBSK7X	Glaucoma/ocular hypertension	9C61	Approved	[13]

Drug(s) Targeting Cholinesterase (BCHE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hexafluronium bromide	DMFY307	Spasm	MB47.3	Approved	[14]
MEPTAZINOL	DMPSB8F	Pain	MG30-MG3Z	Approved	[15]
Eptastigmine	DMTV7ZM	Cognitive impairment	6D71	Phase 3	[16]
Plasma derived human butyrylcholinesterase	DMF3IBC	Neurotoxicity	NE61	Phase 1	[17]
Protexia	DME1Y9W	Alzheimer disease	8A20	Phase 1	[18]
JES-9501	DMYR3IE	Alzheimer disease	8A20	Phase 1	[19]
Tetra-hydro-isoquinoline derivative 3	DMCZA45	N. A.	N. A.	Patented	[20]
Tetra-hydro-isoquinoline derivative 1	DML86IO	N. A.	N. A.	Patented	[20]
Tetra-hydro-isoquinoline derivative 2	DM5CKVF	N. A.	N. A.	Patented	[20]
Tetra-hydro-isoquinoline derivative 4	DMDV0MP	N. A.	N. A.	Patented	[20]

Drug(s) Affected By Amyloid-beta precursor protein (APP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[21]
Selenium	DM25CGV	N. A.	N. A.	Approved	[22]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[23]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[24]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[25]
Penicillamine	DM40EF6	Cystinuria	5C60.2	Approved	[26]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[27]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[28]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[29]
Aluminium	DM6ECN9	Hyperhidrosis	EE00	Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Acetylcholinesterase (AChE)	TT1RS9F	ACES_HUMAN	Inhibitor	[2]
Cholinesterase (BCHE)	TTEB0GD	CHLE_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Protein Interaction/Cellular Processes	[3]

References

• [1] Neurotrophic and neuroprotective actions of (-)- and (+)-phenserine, candidate drugs for Alzheimer's disease. PLoS One. 2013;8(1):e54887.
• [2] 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.
• [3] The integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5'-untranslated region. Ann N Y Acad Sci. 2004 Dec;1035:34-48. doi: 10.1196/annals.1332.003.
• [4] 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.
• [5] 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).
• [6] 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.
• [7] [From symptomatic to disease modifying therapy Recent developments in the pharmacotherapy of Alzheimer's disease]. Fortschr Neurol Psychiatr. 2009 Jun;77(6):326-33.
• [8] Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia-ischemia. Brain Res. 2002 Sep 13;949(1-2):162-70.
• [9] Screening of acetylcholinesterase inhibitors by CE after enzymatic reaction at capillary inlet. J Sep Sci. 2009 May;32(10):1748-56.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [11] Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens. Neuropsychopharmacology. 2008 Aug;33(9):2158-66.
• [12] 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.
• [13] Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Chem Biol. 2003 Jun;10(6):491-502.
• [14] Synergistic effect of acidosis and succinylcholine-induced hyperkalemia in spinal cord transected rats. Acta Anaesthesiol Scand. 1984 Feb;28(1):87-90.
• [15] 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.
• [16] Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine. J Med Chem. 2006 Apr 6;49(7):2174-85.
• [17] 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.
• [18] 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.
• [19] Dehydroevodiamine attenuates beta-amyloid peptide-induced amnesia in mice. Eur J Pharmacol. 2001 Feb 16;413(2-3):221-5.
• [20] A patent review of butyrylcholinesterase inhibitors and reactivators 2010-2017.Expert Opin Ther Pat. 2018 Jun;28(6):455-465.
• [21] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [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] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [24] Simvastatin protects neurons from cytotoxicity by up-regulating Bcl-2 mRNA and protein. J Neurochem. 2007 Apr;101(1):77-86. doi: 10.1111/j.1471-4159.2006.04375.x. Epub 2007 Jan 4.
• [25] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [26] Chelation and intercalation: complementary properties in a compound for the treatment of Alzheimer's disease. J Struct Biol. 2000 Jun;130(2-3):209-16. doi: 10.1006/jsbi.2000.4285.
• [27] Increased processing of APLP2 and APP with concomitant formation of APP intracellular domains in BDNF and retinoic acid-differentiated human neuroblastoma cells. J Neurochem. 2005 Nov;95(4):1059-68. doi: 10.1111/j.1471-4159.2005.03440.x. Epub 2005 Sep 7.
• [28] Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq. Arch Toxicol. 2018 Aug;92(8):2517-2531.
• [29] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [30] Synergistic effects of iron and aluminum on stress-related gene expression in primary human neural cells. J Alzheimers Dis. 2005 Nov;8(2):117-27; discussion 209-15. doi: 10.3233/jad-2005-8204.