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

General Information of Drug (ID: DMRYL9X)

• Drug Name: AP-2243 Drug Info
• Synonyms: AP-2243; CHEMBL244416; BDBM50218528; 3-{4-[(benzylethylamino)methyl]phenyl}-6,7-dimethoxychromen-2-one

Indication

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

• Cross-matching ID:
  PubChem CID: 23643351
  TTD Drug ID: DMRYL9X

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 Beta-secretase (BACE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[12]
E-2609	DMTNUJ8	Alzheimer disease	8A20	Phase 3	[13]
verubecestat	DM4CGH5	Alzheimer disease	8A20	Phase 3	[14]
Lanabecestat	DMFJLB6	Alzheimer disease	8A20	Phase 3	[15]
AZD3293	DMJQHXD	Alzheimer disease	8A20	Phase 2/3	[16]
JNJ-54861911	DMGPJ5U	Alzheimer disease	8A20	Phase 2/3	[15]
R-flurbiprofen	DMFIVSR	N. A.	N. A.	Phase 2	[12]
LY2886721	DMV14LM	Alzheimer disease	8A20	Phase 2	[17]
LY3202626	DM7IFNB	Alzheimer disease	8A20	Phase 2	[15]
AZD-3839	DM72FOD	Alzheimer disease	8A20	Phase 1	[18]

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]
Beta-secretase (BACE)	TT8JRS7	NOUNIPROTAC	Inhibitor	[1]

References

• [1] Multi-target-directed coumarin derivatives: hAChE and BACE1 inhibitors as potential anti-Alzheimer compounds. Bioorg Med Chem Lett. 2008 Jan 1;18(1):423-6.
• [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] The geminal dimethyl analogue of Flurbiprofen as a novel Abeta42 inhibitor and potential Alzheimer's disease modifying agent. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2219-23.
• [13] Targeting the beta secretase BACE1 for Alzheimer's disease therapy. Lancet Neurol. 2014 March; 13(3): 319-329.
• [14] BACE1 inhibitor drugs in clinical trials for Alzheimer's disease. Alzheimers Res Ther. 2014 Dec 24;6(9):89.
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] AZD3293 A novel BACE1 inhibitor: safety, tolerability, and effects on plasma and CSF A-beta peptides following single- and multiple-dose administration. Neurobiology of Aging. May 20, 2008.
• [17] Lessons from a BACE1 inhibitor trial: off-site but not off base.Alzheimers Dement.2014 Oct;10(5 Suppl):S411-9.
• [18] Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease. J Biol Chem. 2012 Nov 30;287(49):41245-57.