U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C49H54F2N8O6
Molecular Weight 889.0017
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEDIPASVIR

SMILES

CC(C)[C@@]([H])(C(=O)N1CC2(CC2)C[C@@]1([H])c3ncc(-c4ccc5-c6ccc(cc6C(c5c4)(F)F)-c7ccc8c(c7)[nH]c([C@]9([H])[C@@]%10([H])CC[C@]([H])(C%10)N9C(=O)[C@]([H])(C(C)C)N=C(O)OC)n8)[nH]3)N=C(O)OC

InChI

InChIKey=VRTWBAAJJOHBQU-KMWAZVGDSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=23384816; http://www.ncbi.nlm.nih.gov/pubmed/?term=22314425

Ledipasvir is an inhibitor of the Hepatitis C Virus (HCV) NS5A protein required for viral RNA replication and assembly of HCV virions. Approved in October 2014 by the FDA, ledipasvir and sofosbuvir (tradename Harvoni) are direct-acting antiviral agents indicated for the treatment of HCV genotype 1 with or without cirrhosis.

CNS Activity

Curator's Comment:: Low levels of C14-ledipasvir-derived radioactivity were observed in the CNS

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
141 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
HARVONI

Approved Use

Indicated for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1, 4, 5, or 6 infection

Launch Date

1412899200000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
323 ng/mL
90 mg 1 times / day steady-state, oral
dose: 90 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: [NO STEREO] PSI-7851|[NO STEREO] SOFOSBUVIR
[NO STEREO] LEDIPASVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
531 ng/mL
45 mg 1 times / day multiple, oral
dose: 45 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: [NO STEREO] PSI-7851|[NO STEREO] SOFOSBUVIR
[NO STEREO] LEDIPASVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7290 ng × h/mL
90 mg 1 times / day steady-state, oral
dose: 90 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: [NO STEREO] PSI-7851|[NO STEREO] SOFOSBUVIR
[NO STEREO] LEDIPASVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
9320 ng × h/mL
45 mg 1 times / day multiple, oral
dose: 45 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: [NO STEREO] PSI-7851|[NO STEREO] SOFOSBUVIR
[NO STEREO] LEDIPASVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
47 h
90 mg 1 times / day steady-state, oral
dose: 90 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: [NO STEREO] PSI-7851|[NO STEREO] SOFOSBUVIR
[NO STEREO] LEDIPASVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.2%
90 mg 1 times / day steady-state, oral
dose: 90 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: [NO STEREO] PSI-7851|[NO STEREO] SOFOSBUVIR
[NO STEREO] LEDIPASVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
90 mg 1 times / day multiple, oral
Highest studied dose
dose: 90 mg 1 times / day
route: oral
experiment_type: multiple
dose_type: Highest studied dose
co-adm with
    data_source:
    https://pubmed.ncbi.nlm.nih.gov/22314425
    unhealthy, 49 years
    population: unhealthy
    age: 49 years
    sex: M+F
    food_status:
    n:
    data_source:
    https://pubmed.ncbi.nlm.nih.gov/22314425
    PubMed

    PubMed

    TitleDatePubMed
    Ledipasvir : a novel synthetic antiviral for the treatment of HCV infection.
    2014 Apr
    Changing the face of hepatitis C management - the design and development of sofosbuvir.
    2015
    Fixed-dose combination of sofosbuvir and ledipasvir for the treatment of chronic hepatitis C genotype 1.
    2015 Apr
    Ledipasvir and sofosbuvir: Interferon free therapy for hepatitis C virus genotype 1 infection.
    2015 Feb 12
    Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: Results from the ION-1, -2, and -3 clinical trials.
    2015 Jun
    Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection.
    2015 Mar 24-31
    Interferon-free therapy for hepatitis C: The hurdles amid a golden era.
    2015 Sep
    Patents

    Patents

    Sample Use Guides

    One tablet (90 mg of ledipasvir and 400 mg of sofosbuvir) taken orally once daily with or without food. Recommended treatment duration: treatment-naive with or without cirrhosis: 12 week. Treatment-experienced without cirrhosis: 12 weeks. Treatment-experienced with cirrhosis: 24 weeks. A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease.
    Route of Administration: Oral
    Ledipasvir inhibitory activity in vitro was characterized by EC50 of 0.031, 0.004, 10.8, 10.1 and 0.045 nM against GT1a, GT1b, GT2a, GT31 and GT4a, respectively.
    Name Type Language
    LEDIPASVIR
    DASH   INN   USAN   VANDF   WHO-DD  
    INN   USAN  
    Official Name English
    HARVONI COMPONENT LEDIPASVIR
    Brand Name English
    LEDIPASVIR [VANDF]
    Common Name English
    LEDIPASVIR ACETONATE [JAN]
    Common Name English
    LEDIPASVIR [MI]
    Common Name English
    LEDIPASVIR [INN]
    Common Name English
    LEDIPASVIR COMPONENT OF HARVONI
    Brand Name English
    LEDIPASVIR [WHO-DD]
    Common Name English
    LEDIPASVIR [USAN]
    Common Name English
    GS-5885
    Code English
    LEDIPASVIR [ORANGE BOOK]
    Common Name English
    Classification Tree Code System Code
    WHO-ATC J05AX65
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    NDF-RT N0000191256
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    FDA ORPHAN DRUG 535916
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    EMA ASSESSMENT REPORTS HARVONI (AUTHORIZED: HEPATITIS C, CHRONIC)
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    NCI_THESAURUS C281
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    WHO-ATC J05AP51
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    Code System Code Type Description
    DRUG BANK
    DB09027
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    DRUG CENTRAL
    4899
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    NCI_THESAURUS
    C129019
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    LACTMED
    Ledipasvir
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    NDF-RT
    N0000185503
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY P-Glycoprotein Inhibitors [MoA]
    MERCK INDEX
    M11788
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    EPA CompTox
    1256388-51-8
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    INN
    9796
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    CAS
    1256388-51-8
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    FDA UNII
    013TE6E4WV
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    RXCUI
    1591922
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY RxNorm
    ChEMBL
    CHEMBL2374220
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    EVMPD
    SUB120165
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    PUBCHEM
    67505836
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY
    NDF-RT
    N0000190113
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY Breast Cancer Resistance Protein Inhibitors [MoA]
    WIKIPEDIA
    Ledipasvir
    Created by admin on Sat Jun 26 01:23:55 UTC 2021 , Edited by admin on Sat Jun 26 01:23:55 UTC 2021
    PRIMARY