Details of the Drug

General Information of Drug (ID: DMO2WYX)

• Drug Name: ZT-1
• Synonyms: (5R,9R)-5-(5-Chloro-2-hydroxy-3-methoxybenzylideneamino)-11-ethylidene-7-methyl-1,2,5,6,9,10-hexahydro-5,9-methanocycloocta[b]pyridin-2-one; 180694-97-7

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 410.9
  Topological Polar Surface Area (xlogp); 2.6
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C23H23ClN2O3
  IUPAC Name: (1R,9R,13E)-1-[(5-chloro-2-hydroxy-3-methoxyphenyl)methylideneamino]-13-ethylidene-11-methyl-6-azatricyclo[7.3.1.02,7]trideca-2(7),3,10-trien-5-one
  Canonical SMILES: C/C=C/1\\[C@@H]2CC3=C([C@]1(CC(=C2)C)N=CC4=C(C(=CC(=C4)Cl)OC)O)C=CC(=O)N3
  InChI: InChI=1S/C23H23ClN2O3/c1-4-17-14-7-13(2)11-23(17,18-5-6-21(27)26-19(18)9-14)25-12-15-8-16(24)10-20(29-3)22(15)28/h4-8,10,12,14,28H,9,11H2,1-3H3,(H,26,27)/b17-4+,25-12?/t14-,23+/m0/s1
  InChIKey: UYRWZANUXPUEPQ-OWNLDCJBSA-N
• Cross-matching ID:
  PubChem CID: 135543744
  CAS Number: 180694-97-7
  TTD ID: D05REB

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], [3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Parkinson disease
• ICD Disease Classification: 8A00.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Acetylcholinesterase (AChE)	DTT	ACHE	6.39E-02	-1.07	-1.15

References

• [1] Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease. Acta Pharmacol Sin. 2013 Jul;34(7):976-82.
• [2] A sensitive method for the determination of the novel cholinesterase inhibitor ZT-1 and its active metabolite huperzine A in rat blood using liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2004;18(6):651-6.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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] 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.