General Information of Drug (ID: DM59AZT)

Drug Name
Clotiazepam
Synonyms
Clotiazepamum; Clozan; Distensan; Rise; Rize; Rizen; Tienor; Trecalmo; Veratran; Y 6047; Clotiazepam [INN:JAN]; Clotiazepamum [INN-Latin]; Clozan (TN); Distensan (TN); Rize (TN); Rizen (TN); Trecalmo (TN); Veratran (TN); Y-6047; Clotiazepam (JP15/INN); 2H-Thieno(2,3e)(1,4)-diazepin-2-one, 5-(o-chlorophenyl)-7-ethyl-1,3-dihydro-1-methyl-(8CI); 5-(2-Chlorophenyl)-7-ethyl-1-methyl-1,3-dihydro-2H-thieno(2,3-e)(1,4)diazepin-2-one; 5-(2-chlorophenyl)-7-ethyl-1-methyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepin-2-one; 5-(2-chlorophenyl)-7-ethyl-1-methyl-3H-thieno[2,3-e][1,4]diazepin-2-one; 5-(o-Chlorophenyl)-7-ethyl-1,3-dihydro-1-methyl-2H-thieno(2,3-e)-1,4-diazepin-2-one
Indication
Disease Entry ICD 11 Status REF
Anxiety disorder 6B00-6B0Z Approved [1]
Therapeutic Class
Hypnotics and Sedatives
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 318.8
Topological Polar Surface Area (xlogp) 3.5
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Half-life
The concentration or amount of drug in body reduced by one-half in 4 hours [2]
Metabolism
The drug is metabolized via the hepatic [3]
Chemical Identifiers
Formula
C16H15ClN2OS
IUPAC Name
5-(2-chlorophenyl)-7-ethyl-1-methyl-3H-thieno[2,3-e][1,4]diazepin-2-one
Canonical SMILES
CCC1=CC2=C(S1)N(C(=O)CN=C2C3=CC=CC=C3Cl)C
InChI
InChI=1S/C16H15ClN2OS/c1-3-10-8-12-15(11-6-4-5-7-13(11)17)18-9-14(20)19(2)16(12)21-10/h4-8H,3,9H2,1-2H3
InChIKey
CHBRHODLKOZEPZ-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
2811
ChEBI ID
CHEBI:31425
CAS Number
33671-46-4
DrugBank ID
DB01559
TTD ID
D0R4DP
INTEDE ID
DR0361

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Translocator protein (TSPO) TTPTXIN TSPO_HUMAN Agonist [4]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [5]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [5]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [5]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Substrate [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Drug information of Clotiazepam, 2008. eduDrugs.
2 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4 Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones. Br J Pharmacol. 1989 Nov;98(3):735-40.
5 Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs. Biol Pharm Bull. 2005 Sep;28(9):1711-6.
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 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
16 Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
17 Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
18 Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8.
19 Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping of an inhibitory monoclonal antibody to P450 2C51. Arch Biochem Biophys. 1997 Feb 15;338(2):157-64.
20 Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Chem Res Toxicol. 1996 Mar;9(2):365-73.
21 CYP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsone. Drug Metab Dispos. 2000 Aug;28(8):865-8.
22 Induction of CYP2C genes in human hepatocytes in primary culture. Drug Metab Dispos. 2001 Mar;29(3):242-51.
23 Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. J Pharmacol Exp Ther. 2002 Jun;301(3):945-52.
24 Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96.
25 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
26 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
27 Drugs that may have potential CYP2B6 interactions.
28 Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Xenobiotica. 2007 Jul;37(7):717-24.
29 Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos. 2005 Dec;33(12):1760-4.
30 PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
31 Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.
32 High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
33 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
34 Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
35 CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
36 Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
37 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
38 Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
39 Translocator protein (18 kDa) mediates the pro-growth effects of diazepam on Ehrlich tumor cells in vivo. Eur J Pharmacol. 2010 Jan 25;626(2-3):131-8.
40 Comparison of five benzodiazepine-receptor agonists on buprenorphine-induced mu-opioid receptor regulation. J Pharmacol Sci. 2009 May;110(1):36-46.
41 Effects of the combination of metyrapone and oxazepam on cocaine and food self-administration in rats. Pharmacol Biochem Behav. 2008 Nov;91(1):181-9.
42 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
43 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. (Target id: 2879).
44 New hypnotics: perspectives from sleep physiology. Vertex. 2007 Jul-Aug;18(74):294-9.