Raltegravir (MK-0518)

Raltegravir (MK-0518) is a potent integrase (IN) inhibitor for WT and S217Q PFV IN with IC50 of 90 nM and 40 nM, respectively.

Price Stock Quantity  
In DMSO USD 210 In stock
USD 120 In stock
USD 210 In stock
USD 670 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Raltegravir (MK-0518) Chemical Structure

Raltegravir (MK-0518) Chemical Structure
Molecular Weight: 444.42

Validation & Quality Control

Customer Reviews(1)

Quality Control & MSDS

Related Compound Libraries

Raltegravir (MK-0518) is available in the following compound libraries:

Product Information

  • Compare Integrase Inhibitors
    Compare Integrase Inhibitors
  • Research Area

Product Description

Biological Activity

Description Raltegravir (MK-0518) is a potent integrase (IN) inhibitor for WT and S217Q PFV IN with IC50 of 90 nM and 40 nM, respectively.
Targets IN (WT PFV) IN (S217Q PFV)
IC50 90 nM 40 nM [1]
In vitro PFV IN carrying the S217H substitution is 10-fold less susceptible to Raltegravir with IC50 of 900 nM. PFV IN displays 10% of WT activity and is inhibited by Raltegravir with an IC50 of 200 nM, indicating a ~twofold decrease in susceptibility to the IN strand transfer inhibitor (INSTI) compared with WT IN. S217Q PFV IN is as sensitive to Raltegravir as the WT enzyme. [1] Raltegravir is metabolized by glucuronidation, not hepatically. Raltegravir has potent in vitro activity against HIV-1, with a 95% inhibitory concentration of 31?0 nM, in human T lymphoid cell cultures. Raltegravir is also active against HIV-2 when Raltegravir is tested in CEMx174 cells, with an IC95 of 6 nM. Raltegravir metabolism occurs primarily through glucuronidation. Drugs that are strong inducers of the glucuronidation enzyme, UGT1A1, significantly reduce Raltegravir concentrations and should not be used. Raltegravir exhibits weak inhibitory effects on hepatic cytochrome P450 activity. Raltegravir does not induce CYP3A4 RNA expression or CYP3A4-dependent testosterone 6-β-hydroxylase activity. [2] Raltegravir cellular permeativity is reduced in the presence of magnesium and calcium. [3] Raltegravir and related HIV-1 integrase (IN) strand transfer inhibitors (INSTIs efficiently block viral replication. [4] In acutely infected human lymphoid CD4+ T-cell lines MT-4 and CEMx174, SIVmac251 replication is efficiently inhibited by Raltegravir, which shows an EC90 in the low nanomolar range. [5]
In vivo Raltegravir induces viro-immunological improvement of nonhuman primates with progressing SIVmac251 infection. One non-human primate shows an undetectable viral load following Raltegravir monotherapy. [5]
Features The 1st approved human immunodeficiency virus type 1 (HIV-1) integrase inhibitor.

Protocol(Only for Reference)

Kinase Assay: [1]

PFV integration assay For quantitative strand transfer assays, donor DNA substrate is formed by annealing HPLC grade oligonucleotides 5′-GACTCACTATAGGGCACGCGTCAAAATTCCATGACA and 5′-ATTGTCATG GAATTTTGACGCGTGCCCTATAGTGAGTC. Reactions (40 μL) contains 0.75 μM PFV IN, 0.75 μM donor DNA, 4 nM (300 ng) supercoiled pGEM9-Zf(−) target DNA, 125 mM NaCl, 5 mM MgSO4, 4 μM ZnCl2, 10 mM DTT, 0.8% (vol/vol) DMSO, and 25 mM BisTris propane–HCl, pH 7.45. Raltegravir is added at indicated concentrations. Reactions are initiated by addition of 2 μL PFV IN diluted in 150 mM NaCl, 2 mM DTT, and 10 mM Tris-HCl, pH 7.4, and stopped after 1 hour at 37 °C by addition of 25 mM EDTA and 0.5% (wt/vol) SDS. Reaction products, deproteinized by digestion with 20 μg proteinase K for 30 minutes at 37 °C followed by ethanol precipitation, are separated in 1.5% agarose gels and visualized by staining with ethidium bromide. Integration products are quantified by quantitative real-time PCR, using Platinum SYBR Green qPCR SuperMix and three primers: 5′-CTACTTACTCTAGCTTCCCGGCAAC, 5′-TTCGCCAGTTAATAGTTTGCGCAAC, and 5′-GACTCACTATAGGGCACGCGT. PCR reactions (20 μL) contained 0.5 μM of each primer and 1 μL diluted integration reaction product. Following a 5-min denaturation step at 95 °C, 35 cycles are carried out in a CFX96 PCR instrument, using 10 seconds denaturation at 95 °C, 30 seconds annealing at 56 °C and 1 minutes extension at 68 °C. Standard curves are generated using serial dilutions of WT PFV IN reaction in the absence of INSTI.

Cell Assay: [5]

Cell lines Human MT-4 cells
Concentrations 0.0001-1 μM
Incubation Time 5 days
Method Human MT-4 cells are infected for 2 hours with the SIVmac251, HIV-1 (IIIB) and HIV-2 (CDC 77618) stocks at a multiplicity of infection of, approximately, 0.1. Cells are then washed three times in phosphate buffered saline, and suspended at 5 × 105/mL in fresh culture medium (to primary cells 50 units/mL of IL-2 are added) in 96-well plates, in the presence or absence of a range of triplicate raltegravir concentrations (0.0001 μM -1 μM). Untreated infected and mock-infected controls are prepared too, in order to allow comparison of the data derived from the different treatments. Viral cytopathogeniciy in MT-4 cells is quantitated by the methyl tetrazolium (MTT) method (MT-4/MTT assay) when extensive cell death in control virus-infected cell cultures is detectable microscopically as lack of capacity to re-cluster. The capability of MT-4 cells to form clusters after infection. Briefly, clusters are disrupted by pipetting; and, after 2 hours of incubation at 37 °C, the formation of new clusters is assessed by light microscopy (100 × magnification). Cell culture supernatants are collected for HIV-1 p24 and HIV-2/SIVmac251 p27 core antigen measurement by ELISA. In CEMx174-infected cell cultures, which show a propensity to form syncytia induced by the virus envelope glycoproteins, syncytia are counted, in blinded fashion, by light microscopy for each well at 5 days following infection.

Animal Study: [5]

Animal Models Indian Rhesus macaques
Dosages 50 mg/kg or 100 mg/kg
Administration Oral administration
Solubility 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL
1

References

Chemical Information

Download Raltegravir (MK-0518) SDF
Molecular Weight (MW) 444.42
Formula

C20H21FN6O5

CAS No. 518048-05-0
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Syonnyms Isentress
Solubility (25°C) * In vitro DMSO 89 mg/mL (200 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(2-(2-methyl-1,3,4-oxadiazole-5-carboxamido)propan-2-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide

Preparing Stock Solutions

Stock Solution (1ml DMSO) 1mM 10mM 20mM 30mM
Mass(mg) 0.44442 4.4442 8.8884 13.3326

Research Area

Customer Reviews (1)


Click to enlarge
Rating
Source Vet Microbiol. 2011 Aug 26;152(1-2):165-8 . Raltegravir (MK-0518) purchased from Selleck
Method PCR
Cell Lines QN10, FEA and CrFK cells lines
Concentrations 0.196 nM to 3 uM
Incubation Time 7 d
Results Raltegravir effective 50% inhibitory concentrations (EC50) were of 7.6 nM in QN10, of 1.3 nM in FEA and of 2.2 nM in CrFK cells.

Product Citations (4)

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.

Tel: +1-832-582-8158 Ext:3

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

* Indicates a Required Field

Related Integrase Inhibitors

  • Rilpivirine

    Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI), and used to treat HIV-1 infection.

  • Raltegravir (MK-0518)

    Raltegravir (MK-0518) is a potent integrase (IN) inhibitor for WT and S217Q PFV IN with IC50 of 90 nM and 40 nM, respectively.

    Features:The 1st approved human immunodeficiency virus type 1 (HIV-1) integrase inhibitor.

  • Elvitegravir (GS-9137, JTK-303)

    Elvitegravir (EVG, JTK-303/GS-9137) is an 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.

  • Dolutegravir (GSK1349572)

    S/GSK1349572 (GSK1349572) is a two-metal-binding HIV integrase inhibitor with IC50 of 2.7 nM, modest activity against raltegravir-resistant signature mutants Y143R, Q148K, N155H, and G140S/Q148H. Phase 3.

    Features:A next-generation and two-metal-binding HIV integrase strand transfer inhibitor.

  • BMS-707035

    BMS-707035 is a specific HIV-I integrase (IN) inhibitor with IC50 of 15 nM. Phase 2.

  • MK-2048

    MK-2048 is a potent inhibitor of integrase (IN) and INR263K with IC50 of 2.6 nM and 1.5 nM, respectively.

  • Maraviroc

    Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM, respectively.

  • Tenofovir

    Tenofovir blocks reverse transcriptase and hepatitis B virus infections.

    Features:Tenofovir disoproxil fumarate is the prodrug form of tenofovir.

  • Tenofovir Disoproxil Fumarate

    Tenofovir Disoproxil Fumarate belongs to nucleotide analogue reverse transcriptase inhibitors (nRTIs).

  • Emtricitabine

    Emtricitabine is a nucleoside reverse transcriptase inhibitor with an IC50 of 27.7 μM.

Recently Viewed Items

Tags: buy Raltegravir (MK-0518) | Raltegravir (MK-0518) ic50 | Raltegravir (MK-0518) price | Raltegravir (MK-0518) cost | Raltegravir (MK-0518) solubility dmso | Raltegravir (MK-0518) purchase | Raltegravir (MK-0518) manufacturer | Raltegravir (MK-0518) research buy | Raltegravir (MK-0518) order | Raltegravir (MK-0518) mouse | Raltegravir (MK-0518) chemical structure | Raltegravir (MK-0518) mw | Raltegravir (MK-0518) molecular weight | Raltegravir (MK-0518) datasheet | Raltegravir (MK-0518) supplier | Raltegravir (MK-0518) in vitro | Raltegravir (MK-0518) cell line | Raltegravir (MK-0518) concentration | Raltegravir (MK-0518) nmr
Contact Us