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

General Information of Drug (ID: DM83EBP)

• Drug Name: Alisporivir Drug Info
• Synonyms: DEB-025; Debio-025; HCV infection therapy, Debiopharm/Novartis; HIV infection therapy, Debiopharm

Indication

Disease Entry	ICD 11	Status	REF
Duchenne dystrophy	8C70	Phase 3	[1]
Hepatitis C virus infection	1E51.1	Phase 3	[2]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[3]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[4]

• Cross-matching ID:
  PubChem CID: 11513676
  CAS Number: CAS 254435-95-5
  TTD Drug ID: DM83EBP
  INTEDE Drug ID: DR1885

Molecule-Related Drug Atlas

Drug(s) Targeting Calcium signal-modulating cyclophilin ligand (CAML)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SCY-635	DM1C9NQ	Hepatitis C virus infection	1E51.1	Phase 2	[7]
SCY-641	DMELFBU	Ocular inflammation	9C61.24	Preclinical	[8]
D-43787	DM0YFZ6	Allergy	4A80-4A85	Terminated	[9]

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	[10]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[11]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[12]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[13]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[14]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[16]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[17]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[11]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Calcium signal-modulating cyclophilin ligand (CAML)	TTATDGJ	CAMLG_HUMAN	Inhibitor	[5]
HUMAN cyclophilin A (CYPA)	TTS41ER	PPIA_HUMAN	Inhibitor	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

References

• [1] ClinicalTrials.gov (NCT02465203) 3-year Follow-up Study to Assess the Viral Activity in Hepatitis C Patients Who Failed Feeder DEB025/Alisporivir Study.
• [2] ClinicalTrials.gov (NCT01500772) Alisporivir With PEG and RBV in Protease Inhibitor (PI) Treatment Failure Patients With Chronic Hepatitis C
• [3] Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020 Mar;19(3):149-150.
• [4] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
• [5] DEB025 (Alisporivir) inhibits hepatitis C virus replication by preventing a cyclophilin A induced cis-trans isomerisation in domain II of NS5A. PLoS One. 2010 Oct 27;5(10):e13687.
• [6] Profile of alisporivir and its potential in the treatment of hepatitis C. Drug Des Devel Ther. 2013;7:105-15.
• [7] SCY-635, a novel nonimmunosuppressive analog of cyclosporine that exhibits potent inhibition of hepatitis C virus RNA replication in vitro. Antimicrob Agents Chemother. 2010 Feb;54(2):660-72.
• [8] 2011 Pipeline of SCYNEXIS.
• [9] Anti-inflammatory effects of a cyclosporine receptor-binding compound, D-43787. J Pharmacol Exp Ther. 2002 May;301(2):738-46.
• [10] 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.
• [11] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [12] 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.
• [13] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [14] 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.
• [15] 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.
• [16] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [17] 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.
• [18] 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.