Details of the Drug

General Information of Drug (ID: DM9GZW6)

• Drug Name: Vabicaserin
• Synonyms: Vabicaserin hydrochloride; PF-05208769; PF-5208769; SCA-136; WY-16629

Indication

Disease Entry	ICD 11	Status	REF
Psychotic disorder	6A20-6A25	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 228.33
  Topological Polar Surface Area (xlogp); 2.5
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 2
• Chemical Identifiers:
  Formula: C15H20N2
  IUPAC Name: (12R,16S)-7,10-diazatetracyclo[8.6.1.05,17.012,16]heptadeca-1,3,5(17)-triene
  Canonical SMILES: C1C[C@H]2CN3CCNCC4=C3C(=CC=C4)[C@H]2C1
  InChI: InChI=1S/C15H20N2/c1-3-11-9-16-7-8-17-10-12-4-2-5-13(12)14(6-1)15(11)17/h1,3,6,12-13,16H,2,4-5,7-10H2/t12-,13-/m0/s1
  InChIKey: NPTIPEQJIDTVKR-STQMWFEESA-N
• Cross-matching ID:
  PubChem CID: 11521822
  CAS Number: 887258-95-9
  DrugBank ID: DB12071
  TTD ID: D02BRJ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 2B receptor (HTR2B)	TT0K1SC	5HT2B_HUMAN	Modulator	[2], [3]
5-HT 2C receptor (HTR2C)	TTWJBZ5	5HT2C_HUMAN	Modulator	[2], [3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Psychotic disorder
• ICD Disease Classification: 6A20-6A25

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
5-HT 2C receptor (HTR2C)	DTT	HTR2C	8.66E-01	-0.13	-0.12
5-HT 2B receptor (HTR2B)	DTT	HTR2B	2.08E-01	-0.05	-0.23

References

• [1] ClinicalTrials.gov (NCT00768612) Study Evaluating Safety and Tolerability of Vabicaserin in Patients With Sudden Worsening of Schizophrenia. U.S. National Institutes of Health.
• [2] Prediction of Efficacy of Vabicaserin, a 5-HT2C Agonist, for the Treatment of Schizophrenia Using a Quantitative Systems Pharmacology Model.CPT Pharmacometrics Syst Pharmacol.2014 Apr 23;3:e111.
• [3] Characterization of vabicaserin (SCA-136), a selective 5-hydroxytryptamine 2C receptor agonist. J Pharmacol Exp Ther. 2011 Jun;337(3):673-80.
• [4] Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23.
• [5] Some properties of 5-hydroxytryptamine receptors in the hindquarters of the rat. Br J Pharmacol. 1979 Sep;67(1):79-85.
• [6] Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
• [7] New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300.
• [8] Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
• [9] Novel serotonin receptor 2 (5-HT2R) agonists and antagonists: a patent review (2004-2014).Expert Opin Ther Pat. 2016;26(1):89-106.
• [10] Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
• [11] The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes. Anesth Analg. 2004 May;98(5):1401-6, table of contents.
• [12] Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulatio... Mol Pharmacol. 2008 Mar;73(3):748-57.
• [13] Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005 Sep-Oct;60(5):441-60.
• [14] Spinal serotonin receptor activation modulates the exercise ventilatory response with increased dead space in goats. Respir Physiol Neurobiol. 2008 May 31;161(3):230-8.
• [15] Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
• [16] Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists ... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3708-12.
• [17] SR46349-B, a 5-HT(2A/2C) receptor antagonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Neuropsychopharmacology. 2002 Sep;27(3):430-41.
• [18] The neuropharmacology of sleep paralysis hallucinations: serotonin 2A activation and a novel therapeutic drug. Psychopharmacology (Berl). 2018 Nov;235(11):3083-3091.