Details of the Drug

General Information of Drug (ID: DM1F42Z)

• Drug Name: Oxatomide
• Synonyms: Celtect; Oxatimide; Oxatomida; Oxatomidum; Oxetal; Tinset; CBMicro_024634; KW 4354; O 9387; R 35443; R35443; Celtect (TN); KW-4354; McN-JR 35443; Oxatomida [INN-Spanish]; Oxatomide (tinset); Oxatomidum [INN-Latin]; R 35,443; R-35443; Oxatomide (JAN/USAN/INN); Oxatomide [USAN:BAN:INN:JAN]; 1-(3-(4-(Diphenylmethyl)-1-piperazinyl)propyl)-1,3-dihydro-2H-benzimidazol-2-one; 1-(3-(4-(Diphenylmethyl)-1-piperazinyl)propyl)-2-benzimidazolinone; 1-[3-(4-Benzhydryl-piperazin-1-yl)-propyl]-1,3-dihydro-benzoimidazol-2-one; 1-[3-[4-(Diphenylmethyl)-1-piperazinyl]propyl]-1,3-dihydro-2H-benzimidazol-2-one; 1-[3-[4-(Diphenylmethyl)-1-piperazinyl]propyl]-2-benzimidazolinone; 3-[3-(4-benzhydrylpiperazin-1-yl)propyl]-1H-benzimidazol-2-one

Indication

Disease Entry	ICD 11	Status	REF
Hay fever	CA08.00	Approved	[1]

• Therapeutic Class: Antiallergic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 426.6
  Topological Polar Surface Area (xlogp); 4.1
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
  Elimination: 0% of drug is excreted from urine in the unchanged form [2]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.9321 micromolar/kg/day [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 0.043 mg/mL [2]
• Chemical Identifiers:
  Formula: C27H30N4O
  IUPAC Name: 3-[3-(4-benzhydrylpiperazin-1-yl)propyl]-1H-benzimidazol-2-one
  Canonical SMILES: C1CN(CCN1CCCN2C3=CC=CC=C3NC2=O)C(C4=CC=CC=C4)C5=CC=CC=C5
  InChI: InChI=1S/C27H30N4O/c32-27-28-24-14-7-8-15-25(24)31(27)17-9-16-29-18-20-30(21-19-29)26(22-10-3-1-4-11-22)23-12-5-2-6-13-23/h1-8,10-15,26H,9,16-21H2,(H,28,32)
  InChIKey: BAINIUMDFURPJM-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4615
  ChEBI ID: CHEBI:31943
  CAS Number: 60607-34-3
  DrugBank ID: DB12877
  TTD ID: D0AJ5L
  INTEDE ID: DR1213

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histamine H1 receptor (H1R)	TTTIBOJ	HRH1_HUMAN	Antagonist	[1], [4]

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]

Molecular Expression Atlas of This Drug

• The Studied Disease: Hay fever
• ICD Disease Classification: CA08.00

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Histamine H1 receptor (H1R)	DTT	HRH1	6.74E-01	0.13	0.43
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	8.70E-01	2.98E-02	1.22E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.76E-01	1.26E-01	8.27E-01

References

• [1] Intact cell binding for in vitro prediction of sedative and non-sedative histamine H1-receptor antagonists based on receptor internalization. J Pharmacol Sci. 2008 May;107(1):66-79.
• [2] BDDCS applied to over 900 drugs
• [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] Effects of fexofenadine and other antihistamines on components of the allergic response: adhesion molecules. J Allergy Clin Immunol. 2003 Oct;112(4 Suppl):S78-82.
• [5] Identification of human P450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its kinetic parameters and inhibition constants. Biol Pharm Bull. 2005 Feb;28(2):328-34.
• [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.
• [23] Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol. 2001 Mar;59(3):420-6.
• [24] Clinical research of Ibudilast on treating the steroid resistant allergic rhinitis. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2009 Jan;23(2):63-6.
• [25] Update on prescription and over-the-counter histamine inverse agonists in rhinitis therapy. Curr Allergy Asthma Rep. 2009 Mar;9(2):140-8.
• [26] Central effects of cinnarizine: restricted use in aircrew. Aviat Space Environ Med. 2002 Jun;73(6):570-4.
• [27] Novel therapeutic usage of low-dose doxepin hydrochloride. Expert Opin Investig Drugs. 2007 Aug;16(8):1295-305.
• [28] Influence of epinastine hydrochloride, an H1-receptor antagonist, on the function of mite allergen-pulsed murine bone marrow-derived dendritic cell... Mediators Inflamm. 2009;2009:738038.
• [29] Examining the tolerability of the non-sedating antihistamine desloratadine: a prescription-event monitoring study in England. Drug Saf. 2009;32(2):169-79.