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

General Information of Drug (ID: DMVDQO6)

• Drug Name: AD-35 Drug Info
• Synonyms: 1531586-58-9; 6'-(2-(1-(Pyridin-2-ylmethyl)piperidin-4-yl)ethyl)spiro[cyClopropane-1,5'-[1,3]dioxolo[4,5-f]isoindol]-7'(6'H)-one; starbld0021420; CHEMBL3949886; SCHEMBL15598869; AD-35; BDBM231544; GLXC-15057; IND-120499; US9346818, I-29; US9346818, I-33; US9346818, I-35

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 72707125
  TTD Drug ID: DMVDQO6

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

Drug(s) Targeting Amyloid beta A4 protein (APP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nirogacestat	DMUP5Z0	Desmoid tumour	2F7C	Approved	[13]
Aducanumab	DM51JW4	Alzheimer disease	8A20	Approved	[14]
Lecanemab	DMW03YD	Alzheimer disease	8A20	Approved	[15]
Florbetapir F-18	DMJ8A3Z	Diagnostic imaging	N.A.	Approved	[9]
GV-971	DMTMA5W	Alzheimer disease	8A20	Approved in China	[16]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[17]
Solanezumab	DM0HIU5	Alzheimer disease	8A20	Phase 3	[18]
Tramiprosate	DM7BSRH	Alzheimer disease	8A20	Phase 3	[19]
Bapineuzumab	DMHQ5GK	Alzheimer disease	8A20	Phase 3	[20]
ALZT-OP1	DMG5BTD	Alzheimer disease	8A20	Phase 3	[21]

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]
Amyloid beta A4 protein (APP)	TTE4KHA	A4_HUMAN	Inhibitor	[2]

References

• [1] ClinicalTrials.gov (NCT03790982) A Randomized, Double Blind, Placebo Controlled, Parallel-Group 52-week Multicenter Phase II Study to Investigate the Safety, Efficacy and Pharmacokinetics of AD-35 Tablet in Subjects With Mild to Moderate Alzheimer's Disease. U.S.National Institutes of Health.
• [2] Multifunctional Compound AD-35 Improves Cognitive Impairment and Attenuates the Production of TNF-alpha and IL-1beta in an Abeta25-35-induced Rat Model of Alzheimer's Disease. J Alzheimers Dis. 2017;56(4):1403-1417.
• [3] 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.
• [4] 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).
• [5] 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.
• [6] [From symptomatic to disease modifying therapy Recent developments in the pharmacotherapy of Alzheimer's disease]. Fortschr Neurol Psychiatr. 2009 Jun;77(6):326-33.
• [7] Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia-ischemia. Brain Res. 2002 Sep 13;949(1-2):162-70.
• [8] Screening of acetylcholinesterase inhibitors by CE after enzymatic reaction at capillary inlet. J Sep Sci. 2009 May;32(10):1748-56.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [10] Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens. Neuropsychopharmacology. 2008 Aug;33(9):2158-66.
• [11] 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.
• [12] Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Chem Biol. 2003 Jun;10(6):491-502.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Passive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets . Immun Ageing. 2013; 10: 18.
• [15] The murine version of BAN2401 (mAb158) selectively reduces amyloid-beta protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimers Dis. 2015;43(2):575-88.
• [16] Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression. Cell Res. 2019 Oct;29(10):787-803.
• [17] Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and evaluation for beta-amyloid plaque imaging. J Med Chem. 2006 Oct 5;49(20):6111-9.
• [18] Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014 Jan 23;370(4):311-21.
• [19] Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging. 2007 Apr;28(4):537-47.
• [20] Bapineuzumab: anti-beta-amyloid monoclonal antibodies for the treatment of Alzheimer's disease. Immunotherapy. 2010 Nov;2(6):767-82.
• [21] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)