Details of the Drug

General Information of Drug (ID: DMEO6A5)

• Drug Name: S-9977
• Synonyms: S-9977-2

Indication

Disease Entry	ICD 11	Status	REF
Cognitive impairment	6D71	Discontinued in Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight; 456
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 6
  Hydrogen Bond Donor Count; 1
  Hydrogen Bond Acceptor Count; 5
• Chemical Identifiers:
  Formula: C20H34ClN7O3
  IUPAC Name: N,N-diethyl-4-[3-(1,3,7-trimethyl-2,6-dioxopurin-8-yl)propyl]piperazine-1-carboxamide;hydrochloride
  Canonical SMILES: CCN(CC)C(=O)N1CCN(CC1)CCCC2=NC3=C(N2C)C(=O)N(C(=O)N3C)C.Cl
  InChI: InChI=1S/C20H33N7O3.ClH/c1-6-26(7-2)20(30)27-13-11-25(12-14-27)10-8-9-15-21-17-16(22(15)3)18(28)24(5)19(29)23(17)4;/h6-14H2,1-5H3;1H
  InChIKey: GVHZRDKDUVIRNY-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 132156
  CAS Number: 138472-18-1
  TTD ID: D0F3FB

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]

Molecular Expression Atlas of This Drug

• The Studied Disease: Cognitive impairment
• ICD Disease Classification: 6D71

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] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001724)
• [2] Xanthine derivatives IBMX and S-9977-2 potentiate transmission at an Aplysia central cholinergic synapse. Brain Res. 1992 Jul 17;586(1):78-85.
• [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.