Details of the Drug

General Information of Drug (ID: DMBG0N4)

• Drug Name: Cibenzoline
• Synonyms: Cibenzolina; Cibenzolina [INN-Spanish]; Cibenzoline; Cibenzoline (INN); Cibenzoline [INN]; Cibenzolinum; Cibenzolinum [INN-Latin]; Cifenline; Cifenline (USAN); Cifenline [USAN]; Ro 22-7796; Ro 227796; UP 33901; (+-)-2-(2,2-Diphenylcyclopropyl)-2-imidazoline; 1H-Imidazole, 2-(2,2-diphenylcyclopropyl)-4,5-dihydro-, (+-)-; 2-(2,2-Diphenyl-cyclopropyl)-4,5-dihydro-1H-imidazole; 2-(2,2-diphenylcyclopropyl)-2-imidazoline; 2-(2,2-diphenylcyclopropyl)-4,5-dihydro-1H-imidazole; 53267-01-9; C18H18N2; CHEMBL87045; EINECS 258-453-7

Indication

Disease Entry	ICD 11	Status	REF
Atrial fibrillation	BC81.3	Phase 4	[1]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 262.3
  Topological Polar Surface Area (xlogp); 2.7
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property:
  Bioavailability: 86% of drug becomes completely available to its intended biological destination(s) [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 8.6 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 7.3 hours [3]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 24.77535 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.5% [3]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 4.1 L/kg [3]
• Chemical Identifiers:
  Formula: C18H18N2
  IUPAC Name: 2-(2,2-diphenylcyclopropyl)-4,5-dihydro-1H-imidazole
  Canonical SMILES: C1CN=C(N1)C2CC2(C3=CC=CC=C3)C4=CC=CC=C4
  InChI: IPOBOOXFSRWSHL-UHFFFAOYSA-N
  InChIKey: 1S/C18H18N2/c1-3-7-14(8-4-1)18(15-9-5-2-6-10-15)13-16(18)17-19-11-12-20-17/h1-10,16H,11-13H2,(H,19,20)
• Cross-matching ID:
  PubChem CID: 2747
  ChEBI ID: CHEBI:135083
  CAS Number: 53267-01-9
  DrugBank ID: DB13358
  INTEDE ID: DR0318

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[5]

References

• [1] ClinicalTrials.gov (NCT00540787) A Comparison of Antiarrhythmic Drug Therapy and Radio Frequency Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation.
• [2] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [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] Stereoselective metabolism of cibenzoline, an antiarrhythmic drug, by human and rat liver microsomes: possible involvement of CYP2D and CYP3A. Drug Metab Dispos. 2000 Sep;28(9):1128-34.
• [6] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [7] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [8] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [9] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [10] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [11] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [12] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [13] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [14] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [15] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [16] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [17] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [18] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [19] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [20] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [21] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [22] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.