| Description | MK-2048 is a potent inhibitor of integrase (IN) and INR263K with IC50 of 2.6 nM and 1.5 nM, respectively. |
| In vitro | MK-2048以75 nM和80 nM的IC50抑制B型和C型整合酶活性。高浓度的MK-2048能相当程度地阻止B型和C型酶的解聚。R263K位点的突变轻微增加了整合酶对MK-2048的敏感性。而G118R降低了整合酶活性，导致对MK-2048的抗性增加。[2] MK-2048对S217H整合体的IC50为900 nM。相比之下，MK2048对N224H整合体保持完全活性，IC50为25 nM。与另一种整合酶抑制剂raltegravir相比，MK2048显示出显著较低的解离率。[3] 随后的E138K选择性部分恢复了复制能力，大约为野生型的13%，并使对MK-2048的抗性增加了约8倍。MK-2048对RAL和EVG耐药的病毒有效。经MK-2048暴露后，19周时G118R可能成为新的抗性突变。持续的MK-2048压力导致29周后在IN基因内的E138K位置出现额外的替代。尽管G118R突变仅对MK-2048表现轻微抗性，对RAL或EVG并无影响，但其存在显著降低了与野生型NL4-3相比的病毒复制能力。E138K既部分恢复了病毒复制能力，也增加了对MK-2048的抗性水平。[4] |
| Cell experiments | A total of 7.5×104 PM1 cells per well are infected with clonal NL4-3 virus containing the integrase mutations G118R, E138K, or G118R and E138K or with wild-type viruses (45 ng p24 virus per well) by spinoculation at 1,200 × g for 2 hours at 37 °C. Cells are washed twice to remove unbound virus and then resuspends in RPMI growth medium alone or containing various concentrations of MK-2048, ranging between 0.0256 nM and 2 μM. Experiments is performed, each in duplicate. Supernatant reverse transcriptase (RT) activity is measured at 72 hours postinfection as an indicator of virus replication. Data are normalized based on uninfected and no-drug controls included in each experiment. Viral replication capacity is determined in PM1 cells using the same methodology as that used to determine EC50s, by comparing levels of supernatant RT activity of each mutant virus to those of wild-type virus in the absence of MK-2048.(Only for Reference) |
| Target activity | Integrase (R263K):1.5 nM, Integrase:2.6 nM |
| Synonyms | MK2048 |
| molecular weight | 461.87 |
| Molecular formula | C21H21ClFN5O4 |
| CAS | 869901-69-9 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 9 mg/mL (19.48 mM) H2O: <1 mg/mL Ethanol: <1 mg/mL |
| References | 1. Quashie PK, et al. J Virol. 2012, 86(5), 2696-2705. 2. Bar-Magen T, et al. Retrovirology. 2009, 6, 103. 3. Hare S, et al. Proc Natl Acad Sci U S A. 2010, 107(46), 20057-220062. 4. Bar-Magen T, et al. J Virol. 2010, 84(18), 9210-9216. |