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

General Information of Drug (ID: DMQTUH8)

• Drug Name: CALANOLIDE A Drug Info
• Synonyms: NSC-675451; NSC-664737 (racemate); (+)-(10R,11S,12S)-12-Hydroxy-6,6,10,11-tetramethyl-4-propyl-6,10,11,12-tetrahydro-2H-benzo[1,2-b:3,4-b':5,6-b'']tripyran-2-one; (+)-Calanolide A

Indication

Disease Entry	ICD 11	Status	REF
Mycobacterium infection	1B10-1B21	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 64972
  ChEBI ID: CHEBI:65552
  CAS Number: CAS 142632-32-4
  TTD Drug ID: DMQTUH8
  INTEDE Drug ID: DR0258

Molecule-Related Drug Atlas

Drug(s) Targeting Human immunodeficiency virus Reverse transcriptase (HIV RT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[4]
Nevirapine	DM6HX9B	Human immunodeficiency virus infection	1C62	Approved	[5]
Zalcitabine	DMH7MUV	Human immunodeficiency virus infection	1C62	Approved	[6]
Tenofovir	DM1IS6U	Chronic hepatitis B virus infection		Approved	[4]
Lamivudine	DMI347A	Chronic HBV infection	1E51.0Z	Approved	[7]
Abacavir	DMMN36E	Human immunodeficiency virus infection	1C62	Approved	[8]
Delavirdine	DM3NF5G	Human immunodeficiency virus infection	1C62	Approved	[7]
Efavirenz	DMC0GSJ	Human immunodeficiency virus infection	1C62	Approved	[7]
Rilpivirine	DMJ0QOW	Human immunodeficiency virus infection	1C62	Approved	[9]
Etravirine	DMGV8QU	Human immunodeficiency virus-1 infection	1C62	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
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

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

References

• [1] ClinicalTrials.gov (NCT00005120) The Safety and Effectiveness of (+)-Calanolide A in HIV-Infected Patients Who Have Never Taken Anti-HIV Drugs. U.S. National Institutes of Health.
• [2] Calanolide A: a natural non-nucleoside reverse transcriptase inhibitor. BETA. 1999 Apr;12(2):8-9.
• [3] Metabolism of F18, a derivative of calanolide A, in human liver microsomes and cytosol. Front Pharmacol. 2017 Jul 19;8:479.
• [4] Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33.
• [5] HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism.Nat Struct Mol Biol.2012 Jan 22;19(2):253-9.
• [6] A peptide inhibitor of HIV-1 reverse transcriptase using alpha,beta-dehydro residues: a structure-based computer model. J Biomol Struct Dyn. 1998 Oct;16(2):347-54.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Quadruple nucleos(t)ide reverse transcriptase inhibitors-only regimen of tenofovir plus zidovudine/lamivudine/abacavir in heavily pre-treated HIV-1 infected patients: salvage therapy or backbone only Curr HIV Res. 2009 May;7(3):320-6.
• [9] Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
• [10] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [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.