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

Details

Stereochemistry ABSOLUTE
Molecular Formula C23H23ClFNO5
Molecular Weight 447.8846
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ELVITEGRAVIR

SMILES

CC(C)[C@@]([H])(CO)n1cc(c(=O)c2cc(Cc3cccc(c3F)Cl)c(cc21)OC)C(=O)O

InChI

InChIKey=JUZYLCPPVHEVSV-LJQANCHMSA-N
InChI=1S/C23H23ClFNO5/c1-12(2)19(11-27)26-10-16(23(29)30)22(28)15-8-14(20(31-3)9-18(15)26)7-13-5-4-6-17(24)21(13)25/h4-6,8-10,12,19,27H,7,11H2,1-3H3,(H,29,30)/t19-/m1/s1

HIDE SMILES / InChI
Elvitegravir is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor used in combination with cobicistat, emtricitabine and tenofovir alafenamid (GENVOYA®) for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults. Because integrase is necessary for viral replication, inhibition prevents the integration of HIV-1 DNA into the host genome and thereby blocks the formation of the HIV-1 provirus and resulting propagation of the viral infection.

Originator

Curator's Comment:: A 2005 license agreement between Japan Tobacco, Inc. and Gilead Sciences led to the clinical development of elvitegravir.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.004 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
GENVOYA

Approved Use

GENVOYA is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of GENVOYA.

Launch Date

1.44659526E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.2 μg/mL
85 mg 1 times / day steady-state, oral
dose: 85 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
ELVITEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
18 μg × h/mL
85 mg 1 times / day steady-state, oral
dose: 85 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
ELVITEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.7 h
85 mg 1 times / day steady-state, oral
dose: 85 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
ELVITEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
85 mg 1 times / day steady-state, oral
dose: 85 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
ELVITEGRAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Doses

Doses

DosePopulationAdverse events​
800 mg 2 times / day steady, oral
Highest studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: steady
Dose: 800 mg, 2 times / day
Sources:
unhealthy, 39 years
n = 6
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 39 years
Sex: M+F
Population Size: 6
Sources:
Other AEs: Muscle spasm...
Other AEs:
Muscle spasm (grade 3, 1 patient)
Sources:
85 mg 1 times / day steady, oral
Recommended
Dose: 85 mg, 1 times / day
Route: oral
Route: steady
Dose: 85 mg, 1 times / day
Co-administed with::
ritonavir(100 mg, 1 time per day)
Atazanavir(300 mg orally once daily)
Sources:
unhealthy, 45 years (range: 19–78 years)
n = 354
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 45 years (range: 19–78 years)
Sex: M+F
Population Size: 354
Sources:
Disc. AE: Diarrhea...
AEs leading to
discontinuation/dose reduction:
Diarrhea
Sources:
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
healthy
n = 6
Health Status: healthy
Sex: M
Population Size: 6
Sources:
AEs

AEs

AESignificanceDosePopulation
Muscle spasm grade 3, 1 patient
800 mg 2 times / day steady, oral
Highest studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: steady
Dose: 800 mg, 2 times / day
Sources:
unhealthy, 39 years
n = 6
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 39 years
Sex: M+F
Population Size: 6
Sources:
Diarrhea Disc. AE
85 mg 1 times / day steady, oral
Recommended
Dose: 85 mg, 1 times / day
Route: oral
Route: steady
Dose: 85 mg, 1 times / day
Co-administed with::
ritonavir(100 mg, 1 time per day)
Atazanavir(300 mg orally once daily)
Sources:
unhealthy, 45 years (range: 19–78 years)
n = 354
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 45 years (range: 19–78 years)
Sex: M+F
Population Size: 354
Sources:
PubMed

PubMed

TitleDatePubMed
Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells.
2000 Jan 28
Novel HIV-1 integrase inhibitors derived from quinolone antibiotics.
2006 Mar 9
In-Silico docking of HIV-1 integrase inhibitors reveals a novel drug type acting on an enzyme/DNA reaction intermediate.
2007 Mar 20
Mirabamides A-D, depsipeptides from the sponge Siliquariaspongia mirabilis that inhibit HIV-1 fusion.
2007 Nov
Raltegravir: first in class HIV integrase inhibitor.
2008 Apr
HIV-1 drug resistance mutations: an updated framework for the second decade of HAART.
2008 Apr-Jun
Integrase and integration: biochemical activities of HIV-1 integrase.
2008 Dec 17
Integrase inhibitors: a new treatment option for patients with human immunodeficiency virus infection.
2008 Jan
Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137).
2008 Jan
Genetic diversity of integrase (IN) sequences in antiretroviral treatment-naive and treatment-experienced HIV type 2 patients.
2008 Jul
Integrase inhibitors: a clinical review of raltegravir and elvitegravir.
2008 Jun
Pharmacologic characteristics of investigational and recently approved agents for the treatment of HIV.
2008 May
HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro.
2008 Nov
Effect of ritonavir-boosted tipranavir or darunavir on the steady-state pharmacokinetics of elvitegravir.
2008 Oct 1
Phase III trial begins for elvitegravir.
2008 Sep
Emerging antiviral drugs.
2008 Sep
Clade-specific HIV-1 integrase polymorphisms do not reduce raltegravir and elvitegravir phenotypic susceptibility.
2008 Sep 12
Comparing two integrase inhibitors. The first head-to-head study comparing raltegravir and elvitegravir.
2008 Sep-Oct
Pharmacologic and nonpharmacologic options for the management of HIV infection during pregnancy.
2009
Drug interactions with new and investigational antiretrovirals.
2009
Emerging pharmacology: inhibitors of human immunodeficiency virus integration.
2009
Potent inhibitors of HIV-1 integrase display a two-step, slow-binding inhibition mechanism which is absent in a drug-resistant T66I/M154I mutant.
2009 Feb 24
Dose-response of ritonavir on hepatic CYP3A activity and elvitegravir oral exposure.
2009 Jan
Characterization and structural analysis of HIV-1 integrase conservation.
2009 Jan-Mar
Analysis of pol integrase sequences in diverse HIV type 1 strains using a prototype genotyping assay.
2009 Mar
Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency virus type 1 integrase.
2009 Mar
Efavirenz: a decade of clinical experience in the treatment of HIV.
2009 Nov
Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes.
2009 Nov 11
Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy.
2010
Resistance to HIV-1 integrase inhibitors: A structural perspective.
2010 Aug-Oct
Pharmacokinetic interaction of ritonavir-boosted elvitegravir and maraviroc.
2010 Feb
Improving first-line antiretroviral therapy in resource-limited settings.
2010 Jan
Resistance to integrase inhibitors.
2010 Jun 25
Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity.
2010 Mar
Activity of elvitegravir, a once-daily integrase inhibitor, against resistant HIV Type 1: results of a phase 2, randomized, controlled, dose-ranging clinical trial.
2010 Mar 15
Response of a simian immunodeficiency virus (SIVmac251) to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy.
2010 Mar 16
Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviral-treated HIV-1-infected patients, all naive to integrase inhibitors.
2010 Nov
Mutation Q95K enhances N155H-mediated integrase inhibitor resistance and improves viral replication capacity.
2010 Nov
Development of integrase inhibitors of quinolone acid derivatives for treatment of AIDS: an overview.
2010 Oct
Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor.
2010 Sep
HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays.
2010 Sep 10
Review of the safety, efficacy, and pharmacokinetics of elvitegravir with an emphasis on resource-limited settings.
2012
Patents

Sample Use Guides

One GENVOYA® tablet taken orally once daily with food.
Route of Administration: Oral
It was found that integrase inhibitor elvitegravir interfered with the physiological functions of RAG1, a critical enzyme involved in V(D)J recombination. Circular dichroism studies demonstrated a distinct change in the secondary structure of RAG1 central domain (RAG1 shares DDE motif amino acids with integrases), and when incubated with elvitegravir, an equilibrium dissociation constant (Kd) of 32.53±2.9 uM was determined by biolayer interferometry, leading to inhibition of its binding to DNA. Besides, using extrachromosomal assays, it was shown that elvitegravir inhibited both coding and signal joint formation in pre-B cells. Importantly, treatment with elvitegravir resulted in significant reduction of mature B lymphocytes in 70% of mice studied.
Name Type Language
ELVITEGRAVIR
DASH   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
ELVITEGRAVIR COMPONENT OF STRIBILD
Brand Name English
GS-9137
Code English
ELVITEGRAVIR [VANDF]
Common Name English
ELVITEGRAVIR [MI]
Common Name English
JTK-303
Code English
3-QUINOLINECARBOXYLIC ACID, 6-((3-CHLORO-2-FLUOROPHENYL)METHYL)-1,4-DIHYDRO-1-((1S)-1-(HYDROXYMETHYL)-2-METHYLPROPYL)-7-METHOXY-4-OXO-
Common Name English
ELVITEGRAVIR COMPONENT OF VITEKTA
Brand Name English
ELVITEGRAVIR COMPONENT OF GENVOYA
Brand Name English
ELVITEGRAVIR [USAN]
Common Name English
6-(3-CHLORO-2-FLUOROBENZYL)-1-((1S)-1-(HYDROXYMETHYL)-2-METHYLPROPYL)-7-METHOXY-4-OXO-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID
Systematic Name English
ELVITEGRAVIR [INN]
Common Name English
ELVITEGRAVIR [WHO-DD]
Common Name English
VITEKTA COMPONENT ELVITEGRAVIR
Brand Name English
ELVITEGRAVIR [ORANGE BOOK]
Common Name English
STRIBILD COMPONENT ELVITEGRAVIR
Brand Name English
ELVITEGRAVIR [MART.]
Common Name English
6-(3-CHLORO-2-FLUOROBENZYL)-1-((2S)-1-HYDROXY-3-METHYLBUTAN-2-YL)-7-METHOXY-4-OXO-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID
Systematic Name English
Classification Tree Code System Code
WHO-VATC QJ05AX11
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
WHO-VATC QJ05AR09
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
WHO-ATC J05AR09
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
WHO-ATC J05AX11
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
WHO-ATC J05AR18
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
NDF-RT N0000175887
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
NCI_THESAURUS C281
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
LIVERTOX 345
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
EMA ASSESSMENT REPORTS GENVOYA (AUTHORIZED: HIV INFECTIONS)
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
EMA ASSESSMENT REPORTS VITEKTA (AUTHORIZED: HIV INFECTIONS)
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
Code System Code Type Description
INN
8871
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY
NDF-RT
N0000185507
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY Cytochrome P450 2C9 Inducers [MoA]
PUBCHEM
5277135
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY
EVMPD
SUB69759
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY
FDA UNII
4GDQ854U53
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY
CAS
697761-98-1
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY
NCI_THESAURUS
C76493
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY
RXCUI
1306286
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
4300
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY
DRUG BANK
DB09101
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY
MERCK INDEX
M4880
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY Merck Index
LACTMED
Elvitegravir
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY
ChEMBL
CHEMBL204656
Created by admin on Sat Jun 26 10:05:10 UTC 2021 , Edited by admin on Sat Jun 26 10:05:10 UTC 2021
PRIMARY