ELVITEGRAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H23ClFNO5
Molecular Weight	447.884
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(CC2=CC=CC(Cl)=C2F)C=C3C(=O)C(=CN([C@H](CO)C(C)C)C3=C1)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	447.884
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207561s000lbl.pdf | https://www.drugbank.ca/drugs/DB09101

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 integrase 19 Target ID: CHEMBL3471 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207561s000lbl.pdf	Inhibitor 8146		0.004 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 145 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207561s000lbl.pdf	Primary		Approved 8307	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

C_max

Value	Dose	Co-administered	Analyte	Population
1.2 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203093s000lbl.pdf	85 mg 1 times / day steady-state, oral dose: 85 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	ELVITEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
18 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203093s000lbl.pdf	85 mg 1 times / day steady-state, oral dose: 85 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	ELVITEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203093s000lbl.pdf	85 mg 1 times / day steady-state, oral dose: 85 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	ELVITEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203093s000lbl.pdf	85 mg 1 times / day steady-state, oral dose: 85 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	ELVITEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/16936557	unhealthy, 39 years n = 6 Health Status: unhealthy Condition: HIV-1 infection Age Group: 39 years Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/16936557	Other AEs: Muscle spasm... Other AEs: Muscle spasm (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/16936557
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203093s000lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203093s000lbl.pdf	Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203093s000lbl.pdf
800 mg single, oral Highest studied dose Dose: 800 mg Route: oral Route: single Dose: 800 mg Sources: https://www.natap.org/2006/CROI/CROI_11.htm	healthy n = 6 Health Status: healthy Sex: M Population Size: 6 Sources: https://www.natap.org/2006/CROI/CROI_11.htm	Sources: https://www.natap.org/2006/CROI/CROI_11.htm

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/16936557	unhealthy, 39 years n = 6 Health Status: unhealthy Condition: HIV-1 infection Age Group: 39 years Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/16936557
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203093s000lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203093s000lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:72289	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:72289
ChemicalBook	CB02464875	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02464875
MolPort	MolPort-009-679-398	https://www.molport.com/shop/molecule-link/MolPort-009-679-398
Selleck Chemicals	Elvitegravir	http://www.selleckchem.com/products/Elvitegravir.html
ZINC	ZINC000013682481	http://zinc15.docking.org/substances/ZINC000013682481
eMolecules	32176421	https://www.emolecules.com/cgi-bin/more?vid=32176421

PubMed

Title	Date	PubMed
Pharmacologic and nonpharmacologic options for the management of HIV infection during pregnancy.	2009	22096378
Raltegravir in the management of HIV-infected patients.	2009 Feb 6	19920914
Resistance to novel drug classes.	2009 Nov	20048722
Integrase inhibitors in salvage therapy regimens for HIV-1 infection.	2009 Nov	20048720
Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes.	2009 Nov 11	19906306
In search of second-generation HIV integrase inhibitors: targeting integration beyond strand transfer.	2009 Oct	21426102
Elvitegravir: a new HIV integrase inhibitor.	2009 Oct 19	19843978
Role of etravirine in the management of treatment-experienced patients with human immunodeficiency virus type 1.	2010	22096392
Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy.	2010	21694899
Natural polymorphisms of integrase among HIV type 1-infected South African patients.	2010 Apr	20377427
The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions.	2010 Apr 26	20436677
Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy.	2010 Aug	20300008
Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors.	2010 Aug 31	20807431
Resistance to HIV-1 integrase inhibitors: A structural perspective.	2010 Aug-Oct	20570551
Modeling the HIV-1 Intasome: A Prototype View of the Target of Integrase Inhibitors.	2010 Dec	21994639
Comparison of the Mechanisms of Drug Resistance among HIV, Hepatitis B, and Hepatitis C.	2010 Dec 1	21243082
The HIV-1 integrase α4-helix involved in LTR-DNA recognition is also a highly antigenic peptide element.	2010 Dec 30	21209864
Pharmacokinetic interaction of ritonavir-boosted elvitegravir and maraviroc.	2010 Feb	19851115
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	20055590
Improving first-line antiretroviral therapy in resource-limited settings.	2010 Jan	20046146
Integrase inhibitors: a novel class of antiretroviral agents.	2010 Jan	20040702
Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy.	2010 Jan	19925830
[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	20364666
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	20421122
HIV-1 resistance patterns to integrase inhibitors in antiretroviral-experienced patients with virological failure on raltegravir-containing regimens.	2010 Jun	20388636
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	20519024
Raltegravir: The evidence of its therapeutic value in HIV-1 infection.	2010 Jun 15	20694070
Resistance to integrase inhibitors.	2010 Jun 25	20706558
Anticipating and blocking HIV-1 escape by second generation antiviral shRNAs.	2010 Jun 8	20529316
Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity.	2010 Mar	20043009
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	20146631
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	20233398
Retrovirus Integrase-DNA Structure Elucidates Concerted Integration Mechanisms.	2010 May 1	20882120
Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir.	2010 May 4	20334344
Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviral-treated HIV-1-infected patients, all naive to integrase inhibitors.	2010 Nov	20817922
Mutation Q95K enhances N155H-mediated integrase inhibitor resistance and improves viral replication capacity.	2010 Nov	20736234
Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancer-containing single-tablet fixed-dose combination regimen for the treatment of HIV.	2010 Nov	20683270
Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir.	2010 Nov 29	21114823
Development of integrase inhibitors of quinolone acid derivatives for treatment of AIDS: an overview.	2010 Oct	21044030
Novel integrase inhibitors for HIV.	2010 Sep	20707594
Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor.	2010 Sep	20610719
Novel antiretroviral combinations in treatment-experienced patients with HIV infection: rationale and results.	2010 Sep 10	20731472
HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays.	2010 Sep 10	20647908
Bunyaviridae RNA polymerases (L-protein) have an N-terminal, influenza-like endonuclease domain, essential for viral cap-dependent transcription.	2010 Sep 16	20862319
Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors.	2010 Sep 28	20799722
HIV-1 integrase strand-transfer inhibitors: design, synthesis and molecular modeling investigation.	2011 Feb	21227550
Elvitegravir overcomes resistance to raltegravir induced by integrase mutation Y143.	2011 Jun 1	21505303
Review of the safety, efficacy, and pharmacokinetics of elvitegravir with an emphasis on resource-limited settings.	2012	22347806
Elvitegravir: a once-daily inhibitor of HIV-1 integrase.	2012 Mar	22321026
Pharmacology of HIV integrase inhibitors.	2012 Sep	22789987

Patents

Sample Use Guides

In Vivo Use Guide

One GENVOYA® tablet taken orally once daily with food.

Route of Administration: Oral

In Vitro Use Guide

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 `Sun Dec 18 21:20:47 UTC 2022` Edited by `admin` on `Sun Dec 18 21:20:47 UTC 2022`
Record UNII	4GDQ854U53
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ELVITEGRAVIR

Official Name

English

ELVITEGRAVIR COMPONENT OF STRIBILD

Brand Name

English

GS-9137

Code

English

ELVITEGRAVIR [VANDF]

Common Name

English

Elvitegravir [WHO-DD]

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

VITEKTA COMPONENT ELVITEGRAVIR

Brand Name

English

ELVITEGRAVIR [ORANGE BOOK]

Common Name

English

STRIBILD COMPONENT ELVITEGRAVIR

Brand Name

English

ELVITEGRAVIR [MART.]

Common Name

English

ELVITEGRAVIR [JAN]

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