Raltegravir  (Synonyms: MK-0518)

Raltegravir is a potent integrase (IN) inhibitor, used to treat HIV infection.

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 appr 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±20 nM, in human T lymphoid cell cultures. Raltegravir is also active against HIV-2 when Raltegravir is tested in CEMx174 cells, with an IC₉₅of 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

444.42

C₂₀H₂₁FN₆O₅

518048-05-0

Solid

White to off-white

O=C(C(O)=C(C(NCC1=CC=C(C=C1)F)=O)N=C2C(C)(C)NC(C3=NN=C(C)O3)=O)N2C

Room temperature in continental US; may vary elsewhere.

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Hare, S., et al., Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Proc Natl Acad Sci U S A, 2010. 107(46): p. 20057-62.  [Content Brief]

  [2]. Xu P, et al. Combined Medication of Antiretroviral Drugs Tenofovir Disoproxil Fumarate, Emtricitabine, and Raltegravir Reduces Neural Progenitor Cell Proliferation In Vivo and In Vitro. J Neuroimmune Pharmacol. 2017 Dec;12(4):682-692.  [Content Brief]

  [3]. Hicks C, et al. Raltegravir: the first HIV type 1 integrase inhibitor. Clin Infect Dis. 2009 Apr 1;48(7):931-9  [Content Brief]

  [4]. Moss DM, et al. Divalent metals and pH alter raltegravir disposition in vitro. Antimicrob Agents Chemother. 2012 Jun;56(6):3020-6  [Content Brief]

  [5]. Hare S, et al. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011 Oct;80(4):565-72.  [Content Brief]

  [6]. Lewis, M.G., et al. 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. Retrovirology, 2010. 7: p. 21.  [Content Brief]