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

General Information of Drug (ID: DMNQ869)

• Drug Name: ABT-267 Drug Info
• Synonyms: HCV therapeutic, Abbott

Indication

Disease Entry	ICD 11	Status	REF
Hepatitis C virus infection	1E51.1	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 54767916
  ChEBI ID: CHEBI:85183
  CAS Number: CAS 1258226-87-7
  TTD Drug ID: DMNQ869
  INTEDE Drug ID: DR1193

Molecule-Related Drug Atlas

Drug(s) Targeting Hepatitis C virus Non-structural 5A (HCV NS5A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Daclatasvir	DMSFK9V	Hepatitis C virus infection	1E51.1	Approved	[4]
Glecaprevir; pibrentasvir	DMF6Z5T	Hepatitis C virus infection	1E51.1	Approved	[5]
MK-8742	DMK301H	Hepatitis C virus infection	1E51.1	Phase 3	[6]
Ravidasvir	DM1LFUN	Hepatitis C	1E51	Phase 2/3	[7]
GS-5885	DMSL3DX	Hepatitis C virus infection	1E51.1	Phase 2	[8]
PPI-668	DM4EHVB	Hepatitis C virus infection	1E51.1	Phase 2	[9]
ACH-3102	DM0RPY5	Hepatitis C virus infection	1E51.1	Phase 2	[9]
AZD-2836	DMT2FAP	Hepatitis C virus infection	1E51.1	Phase 1/2	[10]
BMS-824383	DMPQ5XC	Hepatitis C virus infection	1E51.1	Phase 1	[4]
PPI-461	DMTOXLG	Hepatitis C virus infection	1E51.1	Phase 1	[9]

Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[11]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[12]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[13]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[14]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[15]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[16]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[12]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[17]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Hepatitis C virus Non-structural 5A (HCV NS5A)	TTCJ2X8	POLG_HCV1	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C8 (CYP2C8) Main DME	DES5XRU	CP2C8_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT01773070) A Follow up Study Designed to Obtain Long Term Data on Subjects Who Either Achieved a Sustained Virologic Response or or Did Not Achieve a Sustained Virologic Response in an Abbott Sponsored Hepatitis C Study. U.S. National Institutes of Health.
• [2] Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A. J Med Chem. 2014 Mar 13;57(5):2047-57.
• [3] Metabolism and disposition of pan-genotypic inhibitor of hepatitis C virus NS5A ombitasvir in humans. Drug Metab Dispos. 2016 Aug;44(8):1148-57.
• [4] 2011 Pipeline of Bristol-Myers Squibb.
• [5] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [6] Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity. ChemMedChem. 2013 Dec;8(12):1930-40.
• [7] Clinical pipeline report, company report or official report of Presidio Pharmaceuticals.
• [8] Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection. J Med Chem. 2014 Mar 13;57(5):2033-46.
• [9] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [10] TARGETING THE NS5A PROTEIN OF HCV: AN EMERGING OPTION. Drugs Future. 2011 September; 36(9): 691-711.
• [11] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [12] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [13] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [14] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [15] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [16] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [17] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [18] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.