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
Logarithm of the Partition Coefficient (xlogp) 7.4
Rotatable Bond Count (rotbonds) 12
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 10
ADMET Property
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 323 mcg/L []
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 4-4.5 h []
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%) []
Half-life
The concentration or amount of drug in body reduced by one-half in 47 hours []
Metabolism
The drug is metabolized via the human CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 []
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
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

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]
Molecular Interaction Atlas (MIA) 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 DMTI0ZO Moderate Decreased clearance of GS-5885 due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [5]
SODIUM CITRATE DMHPD2Y Moderate Decreased absorption of GS-5885 due to altered gastric pH caused by SODIUM CITRATE. Discovery agent [N.A.] [6]
Ripretinib DM958QB Moderate Decreased clearance of GS-5885 due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [7]
Sodium zirconium cyclosilicate DMCSLZ4 Moderate Decreased absorption of GS-5885 due to altered gastric pH caused by Sodium zirconium cyclosilicate. Hyperkalaemia [5C76] [5]
Naloxegol DML0B41 Minor Decreased clearance of GS-5885 due to the transporter inhibition by Naloxegol. Large intestine motility disorder [DB32] [8]
Ceritinib DMB920Z Moderate Decreased clearance of GS-5885 due to the transporter inhibition by Ceritinib. Lung cancer [2C25] [6]
Artesunate DMR27C8 Moderate Decreased clearance of GS-5885 due to the transporter inhibition by Artesunate. Malaria [1F40-1F45] [6]
GDC-0199 DMH0QKA Major Decreased clearance of GS-5885 due to the transporter inhibition by GDC-0199. Mature B-cell leukaemia [2A82] [7]
Arry-162 DM1P6FR Moderate Decreased clearance of GS-5885 due to the transporter inhibition by Arry-162. Melanoma [2C30] [7]
Rimegepant DMHOAUG Moderate Decreased clearance of GS-5885 due to the transporter inhibition by Rimegepant. Migraine [8A80] [9]
S-297995 DM26IH8 Moderate Decreased clearance of GS-5885 due to the transporter inhibition by S-297995. Opioid use disorder [6C43] [5]
MK-4827 DMLYGH4 Moderate Decreased clearance of GS-5885 due to the transporter inhibition by MK-4827. Ovarian cancer [2C73] [6]
Lefamulin DME6G97 Moderate Decreased clearance of GS-5885 due to the transporter inhibition by Lefamulin. Pneumonia [CA40] [10]
Lusutrombopag DMH6IKO Moderate Decreased clearance of GS-5885 due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [11]
Betrixaban DM2C4RF Moderate Decreased clearance of GS-5885 due to the transporter inhibition by Betrixaban. Venous thromboembolism [BD72] [12]
⏷ 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 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 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
6 Product Information. Harvoni (ledipasvir-sofosbuvir). Gilead Sciences, Foster City, CA.
7 Cerner Multum, Inc. "Australian Product Information.".
8 Product Information. Movantik (naloxegol). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
9 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
10 Product Information. Mavyret (glecaprevir-pibrentasvir). Abbott Pharmaceutical, Abbott Park, IL.
11 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
12 Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.