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

Molecular Formula C23H23ClFNO5
Molecular Weight 447.8846
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Pharmacologic and nonpharmacologic options for the management of HIV infection during pregnancy.
2009
Drug interactions with new and investigational antiretrovirals.
2009
Emerging role of integrase inhibitors in the management of treatment-experienced patients with HIV infection.
2009 Apr
Quinolone carboxylic acids as a novel monoketo acid class of human immunodeficiency virus type 1 integrase inhibitors.
2009 Aug 13
Raltegravir in the management of HIV-infected patients.
2009 Feb 6
Pharmacotherapy of pediatric and adolescent HIV infection.
2009 Jun
Resistance to novel drug classes.
2009 Nov
Integrase inhibitors in salvage therapy regimens for HIV-1 infection.
2009 Nov
Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes.
2009 Nov 11
In search of second-generation HIV integrase inhibitors: targeting integration beyond strand transfer.
2009 Oct
Elvitegravir: a new HIV integrase inhibitor.
2009 Oct 19
Induced-fit docking approach provides insight into the binding mode and mechanism of action of HIV-1 integrase inhibitors.
2009 Sep
Role of etravirine in the management of treatment-experienced patients with human immunodeficiency virus type 1.
2010
Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy.
2010
Natural polymorphisms of integrase among HIV type 1-infected South African patients.
2010 Apr
Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy.
2010 Aug
Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors.
2010 Aug 31
Modeling the HIV-1 Intasome: A Prototype View of the Target of Integrase Inhibitors.
2010 Dec
Comparison of the Mechanisms of Drug Resistance among HIV, Hepatitis B, and Hepatitis C.
2010 Dec 1
The HIV-1 integrase α4-helix involved in LTR-DNA recognition is also a highly antigenic peptide element.
2010 Dec 30
Genetic diversity on the integrase region of the pol gene among HIV type 1-infected patients naive for integrase inhibitors in São Paulo City, Brazil.
2010 Jan
Improving first-line antiretroviral therapy in resource-limited settings.
2010 Jan
Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy.
2010 Jan
Pharmacokinetics and drug-drug interactions of antiretrovirals: an update.
2010 Jan
[Analysis of HIV-1 integrase gene polymorphism in an HIV-infected population from the nosocomial outbreak of HIV infection in the south of Russia in 1989].
2010 Jan-Feb
Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles.
2010 Jul 5
5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention: summary of key research and implications for policy and practice - clinical sciences.
2010 Jun 1
Raltegravir: The evidence of its therapeutic value in HIV-1 infection.
2010 Jun 15
Resistance to integrase inhibitors.
2010 Jun 25
Anticipating and blocking HIV-1 escape by second generation antiviral shRNAs.
2010 Jun 8
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
Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir.
2010 May 4
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
Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancer-containing single-tablet fixed-dose combination regimen for the treatment of HIV.
2010 Nov
Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir.
2010 Nov 29
Development of integrase inhibitors of quinolone acid derivatives for treatment of AIDS: an overview.
2010 Oct
Novel integrase inhibitors for HIV.
2010 Sep
Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor.
2010 Sep
Novel antiretroviral combinations in treatment-experienced patients with HIV infection: rationale and results.
2010 Sep 10
HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays.
2010 Sep 10
Bunyaviridae RNA polymerases (L-protein) have an N-terminal, influenza-like endonuclease domain, essential for viral cap-dependent transcription.
2010 Sep 16
Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors.
2010 Sep 28
HIV-1 integrase strand-transfer inhibitors: design, synthesis and molecular modeling investigation.
2011 Feb
Elvitegravir overcomes resistance to raltegravir induced by integrase mutation Y143.
2011 Jun 1
Review of the safety, efficacy, and pharmacokinetics of elvitegravir with an emphasis on resource-limited settings.
2012
Elvitegravir: a once-daily inhibitor of HIV-1 integrase.
2012 Mar
Pharmacology of HIV integrase inhibitors.
2012 Sep
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.
Substance Class Chemical
Created
by admin
on Sat Jun 26 10:05:10 UTC 2021
Edited
by admin
on Sat Jun 26 10:05:10 UTC 2021
Record UNII
4GDQ854U53
Record Status Validated (UNII)
Record Version
  • Download
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
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> INHIBITOR
INHIBITOR
IC50
Related Record Type Details
METABOLITE LESS ACTIVE -> PARENT
produced by uridine diphosphate glucuronoslytransferase UGT 1A1/3
METABOLITE LESS ACTIVE -> PARENT
Elvitegravir is also metabolized via CYP3A to hydroxy-EVG [metabolite M1]
Related Record Type Details
ACTIVE MOIETY