Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMC3JST)

• Drug Name: Clorazepate Drug Info
• Synonyms: Chlorazepate; Tranxene; Cchlorazepic acid; Chlorazepic acid; Clorazepate dipotassium; Clorazepic acid; Clorazepic acid [BAN]; Gen-xene; Novo-Clopate; Tranxene (Cherazepate dipotasium); Tranxene (TN); Novo-Clopate (TN); (Chloromethyl)(dimethyl)(tridecyloxy)silane; 7-Chloro-2,3-dihydro-2,2-dihydroxy-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acid; 7-chloro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepine-3-carboxylic acid; 7-chloro-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine-3-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Alcohol withdrawal		Approved	[1]
Anxiety		Approved	[1]
Anxiety disorder	6B00-6B0Z	Approved	[2]

• Therapeutic Class: Hypnotics and Sedatives
• Cross-matching ID:
  PubChem CID: 2809
  ChEBI ID: CHEBI:3761
  CAS Number: CAS 23887-31-2
  TTD Drug ID: DMC3JST
  INTEDE Drug ID: DR0358
  ACDINA Drug ID: D00143

Molecule-Related Drug Atlas

Drug(s) Targeting Translocator protein (TSPO)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Diazepam	DM08E9O	Alcohol withdrawal		Approved	[5]
Flunitrazepam	DMGR5Z3	Insomnia	7A00-7A0Z	Approved	[6]
Oxazepam	DMXNZM4	Alcohol withdrawal delirium		Approved	[7]
Midazolam	DMXOELT	Agitation	6A70.3	Approved	[3]
Temazepam	DM02A65	Insomnia	7A00-7A0Z	Approved	[3]
Flumazenil	DMPCG2L	Benzodiazepine overdose	PC91	Approved	[8]
Alprazolam	DMC7XDN	Anxiety		Approved	[6]
Clotiazepam	DM59AZT	Anxiety disorder	6B00-6B0Z	Approved	[9]
Quazepam	DMY4D87	Insomnia	7A00-7A0Z	Approved	[3]
Eszopiclone	DM8RZ9H	Insomnia	7A00-7A0Z	Approved	[10]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[11]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[12]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[18]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[12]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Translocator protein (TSPO)	TTPTXIN	TSPO_HUMAN	Modulator	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

References

• [1] Clorazepate FDA Label
• [2] 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: 7548).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] In vitro drug allergy detection system incorporating human liver microsomes in chlorazepate-induced skin rash: drug-specific proliferation associated with interleukin-5 secretion. Br J Dermatol. 2001 Feb;144(2):316-20.
• [5] 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.
• [6] Comparison of five benzodiazepine-receptor agonists on buprenorphine-induced mu-opioid receptor regulation. J Pharmacol Sci. 2009 May;110(1):36-46.
• [7] 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.
• [8] 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).
• [9] 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.
• [10] New hypnotics: perspectives from sleep physiology. Vertex. 2007 Jul-Aug;18(74):294-9.
• [11] 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.
• [12] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [13] 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.
• [14] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [15] 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.
• [16] 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.
• [17] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [18] 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.
• [19] 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.