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

General Information of Drug (ID: DMSL3DX)

• Drug Name: GS-5885 Drug Info
• Synonyms: Ledipasvir; 1256388-51-8; GS-5885; UNII-013TE6E4WV; GS5885; GS 5885; WHO 9796; Ledipasvir (GS5885); 013TE6E4WV; CHEBI:85089; methyl [(2S)-1-{(6S)-6-[4-(9,9-difluoro-7-{2-[(1R,3S,4S)-2-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}-2-azabicyclo[2.2.1]hept-3-yl]-1H-benzimidazol-5-yl}-9H-fluoren-2-yl)-1H-imidazol-2-yl]-5-azaspiro[2.4]hept-5-yl}-3-methyl-1-oxobutan-2-yl]carbamate; Ledipasvir [USAN:INN]; Ledipasvir (USAN); SCHEMBL2706494; SCHEMBL15116943; CHEMBL2374220; EX-A411; DTXSID90154829; MolPort-039-138-665

Indication

Disease Entry	ICD 11	Status	REF
Hepatitis C virus infection	1E51.1	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 67505836
  ChEBI ID: CHEBI:85089
  CAS Number: CAS 1256388-51-8
  TTD Drug ID: DMSL3DX
  VARIDT Drug ID: DR01290

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	[5]
Glecaprevir; pibrentasvir	DMF6Z5T	Hepatitis C virus infection	1E51.1	Approved	[6]
ABT-267	DMNQ869	Hepatitis C virus infection	1E51.1	Phase 3	[7]
MK-8742	DMK301H	Hepatitis C virus infection	1E51.1	Phase 3	[8]
Ravidasvir	DM1LFUN	Hepatitis C	1E51	Phase 2/3	[9]
PPI-668	DM4EHVB	Hepatitis C virus infection	1E51.1	Phase 2	[10]
ACH-3102	DM0RPY5	Hepatitis C virus infection	1E51.1	Phase 2	[10]
AZD-2836	DMT2FAP	Hepatitis C virus infection	1E51.1	Phase 1/2	[11]
BMS-824383	DMPQ5XC	Hepatitis C virus infection	1E51.1	Phase 1	[5]
PPI-461	DMTOXLG	Hepatitis C virus infection	1E51.1	Phase 1	[10]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[12]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[13]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[14]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[15]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[14]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[14]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]

Drug(s) Affected By Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[19]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[20]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[21]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[22]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[23]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[24]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[25]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[26]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[27]

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 Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Protein Interaction/Cellular Processes	[4]

References

• [1] ClinicalTrials.gov (NCT01435226) GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection. U.S. National Institutesof Health.
• [2] 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.
• [3] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [4] Prospective Drug Candidates as Human Multidrug Transporter ABCG2 Inhibitors: an In Silico Drug Discovery Study. Cell Biochem Biophys. 2021 Jun;79(2):189-200. doi: 10.1007/s12013-021-00985-y. Epub 2021 May 5.
• [5] 2011 Pipeline of Bristol-Myers Squibb.
• [6] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [7] Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A. J Med Chem. 2014 Mar 13;57(5):2047-57.
• [8] Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity. ChemMedChem. 2013 Dec;8(12):1930-40.
• [9] Clinical pipeline report, company report or official report of Presidio Pharmaceuticals.
• [10] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [11] TARGETING THE NS5A PROTEIN OF HCV: AN EMERGING OPTION. Drugs Future. 2011 September; 36(9): 691-711.
• [12] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [13] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [14] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [15] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [16] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [17] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [18] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [19] Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones. Cell Tissue Res. 2012 Aug;349(2):551-63. doi: 10.1007/s00441-012-1417-5. Epub 2012 May 13.
• [20] Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. J Natl Cancer Inst. 2006 Dec 6;98(23):1739-42.
• [21] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [22] ABCG2 polymorphism is associated with the low-density lipoprotein cholesterol response to rosuvastatin. Clin Pharmacol Ther. 2010 May;87(5):558-62.
• [23] Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism. Chem Biol Interact. 2016 Apr 25;250:1-11.
• [24] Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells. Int J Oncol. 2014 Jul;45(1):448-58.
• [25] Activation of beta-catenin signalling by GSK-3 inhibition increases p-glycoprotein expression in brain endothelial cells. J Neurochem. 2008 Aug;106(4):1855-65. doi: 10.1111/j.1471-4159.2008.05537.x. Epub 2008 Jul 4.
• [26] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [27] Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther. 2005 Jul;4(7):747-52.