Details of the Drug

General Information of Drug (ID: DM36C17)

• Drug Name: Blonanserin
• Synonyms: Lonasen; Blonanserin [INN]; AD 5423; AD-5423; Blonanserin (JAN/INN); 2-(4-Ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta(b)pyridine; 2-(4-Ethyl-1-piperazinyl)-4-(p-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta(b)pyridine; 2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine

Indication

Disease Entry	ICD 11	Status	REF
Schizophrenia	6A20	Phase 3	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 367.5
  Logarithm of the Partition Coefficient (xlogp); 5.5
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2 h []
  Clearance: The clearance of drug is 1230 L/h [2]
  Elimination: 57% of blonanserin is excreted in the urine and 30% in the feces [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 10.7 - 16.2 hours [3]
  Metabolism: The drug is metabolized via the CYP3A4 [3]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.93292 micromolar/kg/day [4]
  Vd: The volume of distribution (Vd) of drug is 18060 L [2]
• Chemical Identifiers:
  Formula: C23H30FN3
  IUPAC Name: 2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine
  Canonical SMILES: CCN1CCN(CC1)C2=NC3=C(CCCCCC3)C(=C2)C4=CC=C(C=C4)F
  InChI: InChI=1S/C23H30FN3/c1-2-26-13-15-27(16-14-26)23-17-21(18-9-11-19(24)12-10-18)20-7-5-3-4-6-8-22(20)25-23/h9-12,17H,2-8,13-16H2,1H3
  InChIKey: XVGOZDAJGBALKS-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 125564
  ChEBI ID: CHEBI:31296
  CAS Number: 132810-10-7
  UNII: AQ316B4F8C
  DrugBank ID: DB09223
  TTD ID: D08GJH
  INTEDE ID: DR1902

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Antagonist	[5]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Antagonist	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Schizophrenia
• ICD Disease Classification: 6A20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dopamine D2 receptor (D2R)	DTT	DRD2	2.50E-02	-0.08	-0.49
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-01

References

• [1] 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. (Ligand id: 7670).
• [2] Wen YG, Shang DW, Xie HZ, Wang XP, Ni XJ, Zhang M, Lu W, Qiu C, Liu X, Li FF, Li X, Luo FT: Population pharmacokinetics of blonanserin in Chinese healthy volunteers and the effect of the food intake. Hum Psychopharmacol. 2013 Mar;28(2):134-41. doi: 10.1002/hup.2290. Epub 2013 Feb 18.
• [3] Blonanserin: a review of its use in the management of schizophrenia. CNS Drugs. 2010 Jan;24(1):65-84. doi: 10.2165/11202620-000000000-00000.
• [4] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [5] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [6] Profile of blonanserin for the treatment of schizophrenia. Neuropsychiatr Dis Treat. 2013;9:587-94.