Buy Elvitegravir (GS-9137) | Integrase Inhibitors | Price | IC50

Validation & Quality Control

Product Citations(7)

Cancer Res, 2012, 72(23), 6200-6208

J Virol, 2011, 85(7), 3677-3682

Retrovirology, 2010, 7, 70

J Antimicrob Chemother, 2011, 66(4), 802-812

Antim Ag Ch, 2011, 55(1), 42-49
J Mol Biol, 2011, 410(5):831-46

Virology, 2012, 427(1), 44-50

Customer Reviews(6) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Elvitegravir (GS-9137) is available in the following compound libraries:

Chemical Library (96-well) FDA Approved Drug Library (96-well) Inhibitor Library (96-well)

Product Information

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Elvitegravir (GS-9137) Mechanism
Elvitegravir (GS-9137) Mechanism
Retroviral integrase (IN) contains an N-terminal domain (NTD), which is a three-helical bundle stabilized through binding a Zn atom, and a C-terminal domain (CTD) that adopts an SH3-like fold. ^[1] Three carboxylates of a conserved D,D-35-E motif within the catalytic core domain (CCD) coordinate a pair of divalent metal cations. One asymmetric unit of intasome consists of a single IN dimer, and a pair of symmetry-related IN dimers formed an oblong tetramer with a tightly associated viral DNA molecule. The intermolecular NTD-CCD interactions stabilize the IN dimer-dimer interface. ^[2]
Elvitegravir interacts with and inhibit the DNA-bound form of integrase. Specifically, the metal chelating oxygen atom points towards two divalent Mg cations in the active site, while the halobenzyl groups fits within a tight pocket formed by displacement of the 3’ adenosine (A17). In the pocket, Elvitegravir makes Van der Waals interactions with the bases of the invariant CA dinucleotide, guanine 4 from the non-transferred strand and conserved residues Pro214 and Gln215. In addition, Elvitegravir interacts with Pro214 via its quinolone base and isopropyl group. This mode of drug binding results in displacement of the reactive 3’ viral DNA end from the active site and the following deactivation of the intasome. ^[2]
References
[1] Eijkelenboom AP, et al. Nat Struct Biol. 1995, 2, 807-810.
[2] Hare S, et al. Nature. 2010, 464(7286), 232-236.
Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S2005	Raltegravir (MK-0518)	<1 mg/mL	89 mg/mL	<1 mg/mL
S2001	Elvitegravir (GS-9137)	<1 mg/mL	90 mg/mL	35 mg/mL
S1366	BMS-707035	<1 mg/mL	38 mg/mL	<1 mg/mL
S2765	MK-2048	<1 mg/mL	9 mg/mL	<1 mg/mL
S2667	S/GSK1349572 (GSK1349572)	<1 mg/mL	84 mg/mL	<1 mg/mL

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	Elvitegravir (EVG, JTK-303/GS-9137) is a HIV integrase inhibitor for HIV-1 IIIB, HIV-2 EHO and HIV-2 ROD with IC50 of 0.7 nM, 2.8 nM and 1.4 nM, respectively.
Targets	HIV-1 IIIB	HIV-2 EHO	HIV-2 ROD
IC50	0.7 nM	2.8 nM	1.4 nM ^[1]
In vitro	Elvitegravir inhibits PBMC and PA with IC50 of 0.89 and 20 nM, respectively. Elvitegravir prevents the integration of HIV-1 cDNA through the inhibition of DNA strand transfer. Elvitegravir suppresses the replication of HIV-1, including various subtypes and multiple-drug-resistant clinical isolates, and HIV-2 strains with a 50% effective concentration in the subnanomolar to nanomolar range. Elvitegravir inhibits the replication of HIV-1 clinical isolates carrying NRTI, NNRTI, and PI resistance-associated genotypes. Elvitegravir inhibits the HIV replication at a step that occurs after reverse transcription but before proteolytic cleavage, consistent with the integration step. Elvitegravir inhibits the synthesis of strand transfer products with an IC50 of 54 nM. Elvitegravir blocks integration via the inhibition of IN-mediated strand transfer. ^[1] Elvitegravir inhibits the integration of the HIV-based vector used as a positive control for the luciferase assay with an EC50 of 0.8 nM, as observed in the MAGI assay with HIV-1IIIB. Elvitegravir suppresses the replication of MLV infection with IC50 of 5.8 nM as well as that of the primate retrovirus SIV (IC50 = 0.5 nM), revealing that IN inhibitors have antiviral activity against a broad range of retroviruses. EVG is active against HIV-1 and HIV-2 and has a serum-free antiviral IC50 of 0.3-0.9 nM in peripheral blood mononuclear cells. ^[2]
In vivo
Clinical Trials	Elvitegravir is currengly in a Phase III clinical trial in the treatment of HIV-1 Infection.
Features

Protocol(Only for Reference)

1

References

Chemical Information

Download Elvitegravir (GS-9137) SDF

Molecular Weight (MW)	447.88
Formula	C₂₃H₂₃ClFNO₅
CAS No.	697761-98-1, 697762-15-5 (sodium salt)
Synonyms	N/A

Solubility (25°C) DMSO 90 mg/mL Water <1 mg/mL Ethanol 35 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	(S)-6-(3-chloro-2-fluorobenzyl)-1-(1-hydroxy-3-methylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

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Research Area

Customer Reviews (6)

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Rating

Source

Dr Johanna Weiss of University Hospital Heidelberg. Elvitegravir (GS-9137) purchased from Selleck

Method

Proliferation Assay

Cell Lines

Concentrations

0.01-1000 µM

Incubation Time

Results

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Rating

Source

J Antimicrob Chemother , 2011, 66, 802-812. Elvitegravir (GS-9137) purchased from Selleck

Method

PhA Flow Cytometry Efflux Assay

Cell Lines

MDCKII-BCRP cells

Concentrations

0.001-1000 µM

Incubation Time

Results

Elvitegravir and Vicriviroc increased PhA ﬂuorescence in MDCKII-BCRP cells.

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Rating

Source

J Antimicrob Chemother , 2011, 66, 802-812. Elvitegravir (GS-9137) purchased from Selleck

Method

Calcein assay

Cell Lines

P388/dx cells

Concentrations

0.001-100 µM

Incubation Time

Results

Vicriviroc and Elvitegravir clearly increased calcein ﬂuorescence in P388dx and L-MDR1 cells, but not in the corresponding parental cell lines, which served as negative controls, indicating inhibition of ABCB1.

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Rating

Source

J Antimicrob Chemother , 2011.January, 66:802-812. Elvitegravir (GS-9137) purchased from Selleck

Method

Real-time RT–PCR

Cell Lines

LS180 cells

Concentrations

10 µM

Incubation Time

3 d

Results

For compounds(Elvitegravir, Rifampicin, Rifampicin and Maraviroc) with signiﬁcant induction of ABCB1 mRNA expression at 10 mmol/L, induction was also quantiﬁed at the functional level after 3 days and 1 week of incubation. After 3 days of treatment, a trend towards increased ABCB1 activity was observed for Rifampicin and Elvitegravir. After 7 days ABCB1 activity was signiﬁcantly increased by Elvitegravir, Vicriviroc and the positive control, Rifampicin.

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Rating

Source

Antim Ag Ch, 2011, 55, 42-49. Elvitegravir (GS-9137) purchased from Selleck

Method

Virucidal activity assays

Cell Lines

HeLa-T4 cell

Concentrations

Incubation Time

0-25 h

Results

The addition of AZT could be delayed for about 4.8 h before 50% loss in potency was observed, whereas NVP required about 7.2 h to reveal this effect(Fig. 1A). These data reﬂect the need for AZT conversion to its active phosphorylated form, which NVP does not require. RAL addition could be postponed for about 10.2 h before 50% loss in activity was observed, whereas EVG required about 11.1 h. Titrating RAL and EVG over a 10-fold range (from 10× to 100× the EC95 ) did not signiﬁcantly affect the resulting time windows (10.1 to 12.7 h for 50% inhibition) (Fig. B).

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Rating

Source

Antim Ag Ch, 2011, 55, 42-49. Elvitegravir (GS-9137) purchased from Selleck

Method

virucidal activity assays

Cell Lines

HeLa-T4 cell

Concentrations

1-100 µM

Incubation Time

Results

EFV and EVG inhibited HIV-Luc infectivity, with EC50s of approximately 0.8 and 12 µM, respectively, whereas neither RAL nor NVP displayed signiﬁcant activity.

Product Citations (7)

Targeting the Transposase Domain of the DNA Repair Component Metnase to Enhance Chemotherapy. [Williamson EA, et al. Cancer Res 2012;72(23), 6200-6208]
PubMed: 23090115
Differential sensitivities of retroviruses to integrase strand transfer inhibitors. [Koh Y, et al. J Virol 2011;85(7), 3677-3682]
PubMed: 21270168
Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors. [Smith RA, et al. Retrovirology 2010;7, 70]
PubMed: 20807431

Potential of novel antiretrovirals to modulate expression and function of drug transporters in vitro. [Zembruski NC, et al. J Antimicrob Chemother 2011;66(4), 802-812]
PubMed: 21393174
Identiﬁcation and characterization of persistent intracellular human immunodeﬁciency virus type 1 integrase strand transfer inhibitor activity. [Koh Y, et al. Antim Ag Ch 2011;55(1), 42-49]
PubMed: 21060108
HIV-1 Integrase Strand Transfer Inhibitors Stabilize an Integrase–Single Blunt-Ended DNA Complex. [Bera S, et al. J Mol Biol 2011;410(5):831-46]
PubMed: 21295584
Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir. [Ebina H, et al. Virology 2012;427(1), 44-50]
PubMed: 22374236

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Related Integrase Inhibitors

BMS-707035
BMS-707035 is a specific HIV-I integrase (IN) inhibitor with IC50 of 15 nM.
S/GSK1349572 (GSK1349572)
S/GSK1349572 (GSK1349572) is a two-metal-binding HIV integrase inhibitor with IC50 of 2.7 nM.
MK-2048
MK-2048 is an potent inhibitor of integrase (IN) and IN_R263K with IC50 of 2.6 nM and 1.5 nM, respectively.
Vicriviroc Malate

Vicriviroc (SCH-417690, SCH-D) is a potent CCR5 antagonist with IC50 of 0.91 nM.
Dapivirine
Dapivirine is an nonnucleoside reverse transcriptase inhibitor for HIV reverse transcriptase with IC50 of 24 nM.

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Elvitegravir (GS-9137)

Validation & Quality Control

Product Citations(7)

Customer Reviews(6) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Elvitegravir (GS-9137) is available in the following compound libraries:

Product Information

Compare Integrase Inhibitors

Elvitegravir (GS-9137) Mechanism

Product Description

Biological Activity

Protocol(Only for Reference)

References

Chemical Information

Research Area

Customer Reviews (6)

Product Citations (7)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related Integrase Inhibitors

Proteases and Microbiology Related Products

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Cat.No.	Product Name	Solubility (25°C)
Cat.No.	Product Name	Water	DMSO	Ethanol
S2005	Raltegravir (MK-0518)	<1 mg/mL	89 mg/mL	<1 mg/mL
S2001	Elvitegravir (GS-9137)	<1 mg/mL	90 mg/mL	35 mg/mL
S1366	BMS-707035	<1 mg/mL	38 mg/mL	<1 mg/mL
S2765	MK-2048	<1 mg/mL	9 mg/mL	<1 mg/mL
S2667	S/GSK1349572 (GSK1349572)	<1 mg/mL	84 mg/mL	<1 mg/mL

Choose Your Country or Region

Product Categories

Elvitegravir (GS-9137)

Validation & Quality Control

Product Citations(7)

Customer Reviews(6) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Elvitegravir (GS-9137) is available in the following compound libraries:

Product Information

Compare Integrase Inhibitors

Elvitegravir (GS-9137) Mechanism

Product Description

Biological Activity

Protocol(Only for Reference)

References

Chemical Information

Research Area

Customer Reviews (6)

Product Citations (7)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related Integrase Inhibitors

Proteases and Microbiology Related Products

Recently Viewed Items

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