Details of the Drug

General Information of Drug (ID: DMSL3DX)

Drug Name

GS-5885

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]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 3

Molecular Weight (mw)

889

Topological Polar Surface Area (xlogp)

7.4

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 323 mcg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 4-4.5 h [2]
Elimination: Following a single 90 mg oral dose of [14C]-ledipasvir, mean total recovery of the [14C]-radioactivity in feces and urine was approximately 87%, with most of the radioactive dose recovered from feces (approximately 86%) [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 47 hours [2]
Metabolism: The drug is metabolized via the human CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 [2]

Chemical Identifiers

Formula: C49H54F2N8O6
IUPAC Name: methyl N-[(2S)-1-[(6S)-6-[5-[9,9-difluoro-7-[2-[(1R,3S,4S)-2-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-2-azabicyclo[2.2.1]heptan-3-yl]-3H-benzimidazol-5-yl]fluoren-2-yl]-1H-imidazol-2-yl]-5-azaspiro[2.4]heptan-5-yl]-3-methyl-1-oxobutan-2-yl]carbamate
Canonical SMILES: CC(C)[C@@H](C(=O)N1CC2(CC2)C[C@H]1C3=NC=C(N3)C4=CC5=C(C=C4)C6=C(C5(F)F)C=C(C=C6)C7=CC8=C(C=C7)N=C(N8)[C@@H]9[C@H]1CC[C@H](C1)N9C(=O)[C@H](C(C)C)NC(=O)OC)NC(=O)OC
InChI: InChI=1S/C49H54F2N8O6/c1-24(2)39(56-46(62)64-5)44(60)58-23-48(15-16-48)21-38(58)42-52-22-37(55-42)28-9-13-32-31-12-8-26(18-33(31)49(50,51)34(32)19-28)27-10-14-35-36(20-27)54-43(53-35)41-29-7-11-30(17-29)59(41)45(61)40(25(3)4)57-47(63)65-6/h8-10,12-14,18-20,22,24-25,29-30,38-41H,7,11,15-17,21,23H2,1-6H3,(H,52,55)(H,53,54)(H,56,62)(H,57,63)/t29-,30+,38-,39-,40-,41-/m0/s1
InChIKey: VRTWBAAJJOHBQU-KMWAZVGDSA-N

Cross-matching ID

PubChem CID: 67505836
ChEBI ID: CHEBI:85089
CAS Number: 1256388-51-8
DrugBank ID: DB09027
TTD ID: D06LUZ
VARIDT ID: DR01290

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	[4]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from GS-5885 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Gilteritinib	DMWQ4MZ	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[20]
SODIUM CITRATE	DMHPD2Y	Moderate	Decreased absorption of GS-5885 due to altered gastric pH caused by SODIUM CITRATE.	Discovery agent [N.A.]	[21]
Ripretinib	DM958QB	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[22]
Sodium zirconium cyclosilicate	DMCSLZ4	Moderate	Decreased absorption of GS-5885 due to altered gastric pH caused by Sodium zirconium cyclosilicate.	Hyperkalaemia [5C76]	[20]
Naloxegol	DML0B41	Minor	Decreased clearance of GS-5885 due to the transporter inhibition by Naloxegol.	Large intestine motility disorder [DB32]	[23]
Ceritinib	DMB920Z	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by Ceritinib.	Lung cancer [2C25]	[21]
Artesunate	DMR27C8	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by Artesunate.	Malaria [1F40-1F45]	[21]
GDC-0199	DMH0QKA	Major	Decreased clearance of GS-5885 due to the transporter inhibition by GDC-0199.	Mature B-cell leukaemia [2A82]	[22]
Arry-162	DM1P6FR	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by Arry-162.	Melanoma [2C30]	[22]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[24]
S-297995	DM26IH8	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by S-297995.	Opioid use disorder [6C43]	[20]
MK-4827	DMLYGH4	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by MK-4827.	Ovarian cancer [2C73]	[21]
Lefamulin	DME6G97	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by Lefamulin.	Pneumonia [CA40]	[25]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[26]
Betrixaban	DM2C4RF	Moderate	Decreased clearance of GS-5885 due to the transporter inhibition by Betrixaban.	Venous thromboembolism [BD72]	[27]
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⏷ Show the Full List of 15 DDI Information of This Drug

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	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
3	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
4	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.
5	Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
6	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
7	MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
8	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.
9	Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
10	Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
11	Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
12	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.
13	2011 Pipeline of Bristol-Myers Squibb.
14	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
15	Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A. J Med Chem. 2014 Mar 13;57(5):2047-57.
16	Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity. ChemMedChem. 2013 Dec;8(12):1930-40.
17	Clinical pipeline report, company report or official report of Presidio Pharmaceuticals.
18	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
19	TARGETING THE NS5A PROTEIN OF HCV: AN EMERGING OPTION. Drugs Future. 2011 September; 36(9): 691-711.
20	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
21	Product Information. Harvoni (ledipasvir-sofosbuvir). Gilead Sciences, Foster City, CA.
22	Cerner Multum, Inc. "Australian Product Information.".
23	Product Information. Movantik (naloxegol). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
24	Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
25	Product Information. Mavyret (glecaprevir-pibrentasvir). Abbott Pharmaceutical, Abbott Park, IL.
26	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
27	Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.