| Description | Raltegravir (MK-0518) is a pyrrolidinone derivative and HIV INTEGRASE INHIBITOR that is used in combination with other ANTI-HIV AGENTS for the treatment of HIV INFECTION. |
| In vitro | Raltegravir诱导非人灵长类病毒的免疫学改善,并伴有进展性SIVmac251感染. |
| In vivo | Raltegravir在体外作用于人类T淋巴细胞培养物,有效作用于HIV-1,抑制达95%时浓度为31±20 nM。S217Q PFV IN对Raltegravir的敏感性至少与WT酶相似。在急性感染的人类淋巴CD4 + T细胞系MT-4和CEMx174中,Raltegravir高效抑制SIVmac251复制,EC90处于低纳摩尔范围。Raltegravir微弱抑制肝细胞色素P450。Raltegravir不会诱导CYP3A4 RNA表达或CYP3A4依赖的睾丸激素6-β-羟化酶活性。Raltegravir在镁和钙存在时,细胞扩散性降低。Raltegravir和相关的HIV-1整合酶链转移抑制剂高效阻断病毒复制。 |
| Cell experiments | 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. (Only for Reference) |
| Target activity | Integrase (WT PFV):90 nM, Integrase (S217Q PFV):40 nM |
| Synonyms | 雷特格韦, MK-0518 |
| molecular weight | 444.42 |
| Molecular formula | C20H21FN6O5 |
| CAS | 518048-05-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | H2O: < 1 mg/mL (insoluble or slightly soluble) DMSO: 82 mg/mL (184.5 mM) Ethanol: < 1 mg/mL (insoluble or slightly soluble) |
| References | 1. Hare S, et al. Proc Natl Acad Sci U S A. 2010, 107(46), 20057-220062. 2. Hicks C, et al. Clin Infect Dis. 2009, 48(7), 931-939. 3. Moss DM, et al. Antimicrob Agents Chemother. 2012, 56(6), 3020-3026. 4. Hare S, et al. Mol Pharmacol. 2011, 80(4), 565-572. 5. Lewis MG, et al. Retrovirology. 2010, 7, 21. 6. Tan S, Li W, Li Z, et al. A Novel CXCR4 Targeting Protein SDF-1/54 as an HIV-1 Entry Inhibitor. Viruses. 2019, 11(9): 874. 7. Capoci I R G, Faria D R, Sakita K M, et al. Repurposing approach identifies new treatment options for invasive fungal disease[J]. Bioorganic chemistry. 2019 Mar;84:87-97. 8. Tan S, Li J Q, Cheng H, et al. The anti-parasitic drug suramin potently inhibits formation of seminal amyloid fibrils and their interaction with HIV-1[J]. Journal of Biological Chemistry. 2019: jbc. RA118. 006797. |
| Citations | 1. Tan S, Li J Q, Cheng H, et al. The anti-parasitic drug suramin potently inhibits formation of seminal amyloid fibrils and their interaction with HIV-1. Journal of Biological Chemistry. 2019: jbc. RA118. 006797 2. Capoci I R G, Faria D R, Sakita K M, et al. Repurposing approach identifies new treatment options for invasive fungal disease. Bioorganic Chemistry. 2019 Mar;84:87-97 3. Tan S, Li W, Li Z, et al. A Novel CXCR4 Targeting Protein SDF-1/54 as an HIV-1 Entry Inhibitor. Viruses. 2019, 11(9): 874 |