Details of the Drug

General Information of Drug (ID: DMY9P37)

• Drug Name: Flupenthixol
• Synonyms: Depixol; Emergil; Fluanxol; Fluxanxol; Siplaril; Siplarol; LC 44; N 7009; ALPHA-FLUPENTHIXOL; Cis(Z)Flupenthixol; Cis-Flupenthixol; Cis-Flupentixol; Depixol (TN); Fluanxol (TN); Flupentixol (INN); Flupentixol [INN:DCF]; Flupentixolum [INN-Latin]; Cis-(Z)-Flupenthixol; (Z)-4-(3-(2-(Trifluoromethyl)-9H-thioxanthen-9-ylidene)propyl)-1-piperazineethanol; (Z)-4-(3-(2-(Trifluoromethyl)-9H-thioxanthen-9-ylidene)propyl)piperazine-1-ethanol; 1-Piperazineethanol, 4-(3-(2-(trifluoromethyl)-9H-thioxanthen-9-ylidene)propyl)-(9CI); 2-Trifluoromethyl-9-(3-(4-(2-hydroxyethyl)piperazin-1-yl)propylidene)thioxanthene; 2-Trifluoromethyl-9-(3-(4-(beta-hydroxyethyl)-1-piperazinyl)propylidene)thioxanthene; 2-[4-[(3Z)-3-[2-(Trifluoromethyl)thioxanthen-9-ylidene]propyl]piperazin-1-yl]ethanol; 4-(3-(2-(Trifluoromethyl)-9H-thioxanthen-9-ylidene)propyl)-1-piperazineethanol; 4-(3-(2-(Trifluoromethyl)thioxanthen-9-ylidene)propyl)-1-piperazineethanol

Indication

Disease Entry	ICD 11	Status	REF
Schizophrenia	6A20	Withdrawn from market	[1]

• Therapeutic Class: Antipsychotic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 434.5
  Logarithm of the Partition Coefficient (xlogp); 4.5
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Clearance: The drug present in the plasma can be removed from the body at the rate of 4.14 mL/min/kg [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 34.2 hours [2]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.1 micromolar/kg/day [3]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Tardive dyskinesia	Not Available	DRD2	OTBLXKEG	[4]
Tardive dyskinesia	Not Available	DRD3	OT0OFFKB	[4]
Tardive dyskinesia	Not Available	DRD4	OTAJTO7N	[4]

• Chemical Identifiers:
  Formula: C23H25F3N2OS
  IUPAC Name: 2-[4-[(3Z)-3-[2-(trifluoromethyl)thioxanthen-9-ylidene]propyl]piperazin-1-yl]ethanol
  Canonical SMILES: C1CN(CCN1CC/C=C\\2/C3=CC=CC=C3SC4=C2C=C(C=C4)C(F)(F)F)CCO
  InChI: InChI=1S/C23H25F3N2OS/c24-23(25,26)17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)30-22)5-3-9-27-10-12-28(13-11-27)14-15-29/h1-2,4-8,16,29H,3,9-15H2/b18-5-
  InChIKey: NJMYODHXAKYRHW-DVZOWYKESA-N
• Cross-matching ID:
  PubChem CID: 5281881
  ChEBI ID: CHEBI:10454
  CAS Number: 53772-82-0
  TTD ID: D0OC3J

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Antagonist	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Drug Response	[4]
D(3) dopamine receptor (DRD3)	OT0OFFKB	DRD3_HUMAN	Drug Response	[4]
D(4) dopamine receptor (DRD4)	OTAJTO7N	DRD4_HUMAN	Drug Response	[4]

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

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: 968).
• [2] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [3] 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
• [4] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [5] A role for medial prefrontal dopaminergic innervation in instrumental conditioning. J Neurosci. 2009 May 20;29(20):6599-606.