MD-222 is the first-in-class highly potent PROTAC degrader of MDM2 . MD-222 consists of ligands for Cereblon and MDM2 . MD-222 induces rapid degradation of the MDM2 protein and activation of wild-type p53 in cells. MD-222 has anticancer effects
In Vitro
MD-222 (1-30 nM; 1-2 hours) treatment shows very effective in reducing the levels of MDM2 protein and increasing the levels of p53 in a time- and dose-dependent manner in RS4;11 and RS4;11/IRMI-2 cells. MD-222 (30-100 nM; 6 hours) is effective in increasing the expression of several p53-targeted genes, such as MDM2, CDKN1A, and PUMA in RS4;11 cells, indicating strong activation of p53. MD-222 (4 days) shows cell growth inhibitory activity in RS4;11 cells with an IC50 of 5.5 nM, and has no effect on RS4;11/IRMI-2, MDA-MB-231 and MDA-MB-468 cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: RS4;11 and RS4;11/IRMI-2 cells Concentration: 1 nM, 3 nM, 10 nM, 30 nM Incubation Time: 1 hour, 2 hours Result: Reduced the level of MDM2 and increased the level of p53. RT-PCRCell Line: RS4;11 cells Concentration: 30 nM, 100 nM Incubation Time: 6 hours Result: Increasd the expression of several p53-targeted genes, such as MDM2, CDKN1A, and PUMA.
