Details of the Drug

General Information of Drug (ID: DMUF0BJ)

• Drug Name: CYTISINE
• Synonyms: CYTISINE; 485-35-8; Sophorine; Baptitoxine; (-)-Cytisine; Laburnin; Baptitoxin; Tabex; Ulexin; Cytiton; Ulexine; Tsitizin; Cytitone; Cystisine; Cytizin; Citizin; Tabax; (1R,5S)-3,4,5,6-Tetrahydro-1H-1,5-methanopyrido[1,2-a][1,5]diazocin-8(2H)-one; Baphitoxine; UNII-53S5U404NU; Cytisine (-); HSDB 3560; EINECS 207-616-0; NSC 407282; BRN 0083882; Cytisin; (1r,5s)-1,2,3,4,5,6-Hexahydro-8h-1,5-Methanopyrido[1,2-A][1,5]diazocin-8-One; CHEBI:4055; CHEMBL497939; 53S5U404NU; Cytisine, 98%

Indication

Disease Entry	ICD 11	Status	REF
Tobacco dependence	6C4A.2	Phase 3	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 190.24
  Logarithm of the Partition Coefficient (xlogp); 0.2
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  Clearance: The renal clearance of drug is 43 mL/min []
  Half-life: The concentration or amount of drug in body reduced by one-half in 4.8 hours [2]
  Vd: The volume of distribution (Vd) of drug is 6.2 L/kg []
• Chemical Identifiers:
  Formula: C11H14N2O
  IUPAC Name: (1R,9S)-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one
  Canonical SMILES: C1[C@H]2CNC[C@@H]1C3=CC=CC(=O)N3C2
  InChI: InChI=1S/C11H14N2O/c14-11-3-1-2-10-9-4-8(5-12-6-9)7-13(10)11/h1-3,8-9,12H,4-7H2/t8-,9+/m0/s1
  InChIKey: ANJTVLIZGCUXLD-DTWKUNHWSA-N
• Cross-matching ID:
  PubChem CID: 10235
  ChEBI ID: CHEBI:4055
  CAS Number: 485-35-8
  DrugBank ID: DB09028
  TTD ID: D08XPW

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Neuronal acetylcholine receptor alpha-2 (CHRNA2)	TTF4E0J	ACHA2_HUMAN	Inhibitor	[3]
Neuronal acetylcholine receptor alpha-4 (CHRNA4)	TT4H1MQ	ACHA4_HUMAN	Inhibitor	[4]
Neuronal acetylcholine receptor alpha-7 (CHRNA7)	TTLA931	ACHA7_HUMAN	Inhibitor	[5]
Neuronal acetylcholine receptor beta-2 (CHRNB2)	TT5KPZR	ACHB2_HUMAN	Inhibitor	[4]
Neuronal acetylcholine receptor beta-4 (CHRNB4)	TTTVAFQ	ACHB4_HUMAN	Inhibitor	[6]
Nicotinic acetylcholine receptor (nAChR)	TTJSZTB	NOUNIPROTAC	Antagonist	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4)	OT1H0ZXC	ACHA4_HUMAN	Protein Interaction/Cellular Processes	[7]
Neuronal acetylcholine receptor subunit beta-2 (CHRNB2)	OTNAT2M5	ACHB2_HUMAN	Protein Interaction/Cellular Processes	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Tobacco dependence
• ICD Disease Classification: 6C4A.2

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Neuronal acetylcholine receptor beta-4 (CHRNB4)	DTT	CHRNB4	8.30E-01	9.66E-03	0.06
Neuronal acetylcholine receptor beta-2 (CHRNB2)	DTT	CHRNB2	7.10E-08	-0.15	-0.85
Neuronal acetylcholine receptor alpha-4 (CHRNA4)	DTT	CHRNA4	3.51E-10	-0.15	-0.61

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [3] Synthesis and pharmacological evaluation of novel 9- and 10-substituted cytisine derivatives. Nicotinic ligands of enhanced subtype selectivity. J Med Chem. 2006 May 4;49(9):2673-6.
• [4] Epibatidine isomers and analogues: structure-activity relationships. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5493-7.
• [5] 3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation. Bioorg Med Chem Lett. 2005 Nov 15;15(22):4889-97.
• [6] Deconstructing cytisine: The syntheses of (+/-)-cyfusine and (+/-)-cyclopropylcyfusine, fused ring analogs of cytisine. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2316-9.
• [7] ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties. J Pharmacol Exp Ther. 1997 Oct;283(1):235-46.