Details of the Drug

General Information of Drug (ID: DMMP65N)

• Drug Name: Sertindole
• Synonyms: SerLect; Serdolect; Sertindol; Sertindolum; Sertindole hydrochloride; Lu 23-174; S-1991; SerLect (TN); Serdolect (TN); Serlect (TN); Sertindol [INN-Spanish]; Sertindole [USAN:INN]; Sertindolum [INN-Latin]; Lu-23-174; Sertindole (USAN/INN); 1-(2-(4-(5-Chloro-1-(4-fluorophenyl)-1H-indole-3-yl)-1-piperidinyl)ethyl)-2-imidazolidinone; 1-(2-(4-(5-Chloro-1-(p-fluorophenyl)indol-3-yl)piperidino)ethyl)-2-imidazolidinone; 1-(2-(4-(5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl)-1-piperidinyl)ethyl)-2-imidazolidinone; 1-(2-{4-[5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]piperidin-1-yl}ethyl)imidazolidin-2-one; 1-[2-[4-[5-Chloro-1-(p-fluorophenyl)indol-3-yl]piperidino]ethyl]-2-imidazolidinone; 1-[2-[4-[5-chloro-1-(4-fluorophenyl)-indol-3-yl]-1-piperidyl]ethyl]imidazolidin-2-one; 1-[2-[4-[5-chloro-1-(4-fluorophenyl)indol-3-yl]piperidin-1-yl]ethyl]imidazolidin-2-one

Indication

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Schizophrenia	6A20	Withdrawn from market	[1]

• Therapeutic Class: Antipsychotic Agents
• Affected Organisms: Humans and other mammals
• ATC Code:
  N05AE03: Sertindole
  N05AE: Indole derivatives
  N05A: ANTIPSYCHOTICS
  N05: PSYCHOLEPTICS
  N: NERVOUS SYSTEM
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 440.9
  Logarithm of the Partition Coefficient (xlogp); 4.1
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  Absorption: The drug is orally available []
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
  Bioavailability: 74% of drug becomes completely available to its intended biological destination(s) [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 3 days [4]
  Metabolism: The drug is metabolized via the hepatic []
• Chemical Identifiers:
  Formula: C24H26ClFN4O
  IUPAC Name: 1-[2-[4-[5-chloro-1-(4-fluorophenyl)indol-3-yl]piperidin-1-yl]ethyl]imidazolidin-2-one
  Canonical SMILES: C1CN(CCC1C2=CN(C3=C2C=C(C=C3)Cl)C4=CC=C(C=C4)F)CCN5CCNC5=O
  InChI: InChI=1S/C24H26ClFN4O/c25-18-1-6-23-21(15-18)22(16-30(23)20-4-2-19(26)3-5-20)17-7-10-28(11-8-17)13-14-29-12-9-27-24(29)31/h1-6,15-17H,7-14H2,(H,27,31)
  InChIKey: GZKLJWGUPQBVJQ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 60149
  ChEBI ID: CHEBI:9122
  CAS Number: 106516-24-9
  UNII: GVV4Z879SP
  DrugBank ID: DB06144
  TTD ID: D0OS6O
  VARIDT ID: DR00815
  INTEDE ID: DR1475

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-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[7]

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 2D6 (CYP2D6)	DME	CYP2D6	7.30E-01	-1.91E-02	-1.41E-01
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: 98).
• [2] BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
• [3] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Effect of sertindole on extracellular dopamine, acetylcholine, and glutamate in the medial prefrontal cortex of conscious rats: a comparison with r... Psychopharmacology (Berl). 2009 Sep;206(1):39-49.
• [6] Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin Pharmacol Toxicol. 2007 Jan;100(1):4-22.
• [7] Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. J Pharmacol Exp Ther. 2006 Mar;316(3):1098-106. doi: 10.1124/jpet.105.093393. Epub 2005 Nov 8.