MD-224 (C09-1152-882)

MD-224 is a first-in-class and highly potent small-molecule human murine double minute 2 ( MDM2 ) degrader based on the proteolysistargeting chimera (PROTAC) concept. MD-224 consists of ligands for Cereblon and MDM2 . MD-224 induces rapid degradation of MDM2 at concentrations <1 nM in human leukemia cells, and achieves an IC 50 value of 1.5 nM in inhibition of growth of RS4;11 cells. MD-224 has the potential to be a new class of anticancer agentIn VitroMD-224 (1-30 nM; 2 hours) effectively induces depletion of MDM2 protein and concurrently accumulation of p53 protein in a dose-dependent manner in RS4;11 cells. MD-224 (30 nM; 6 hours) is more potent than MI-1061 in induction of transcriptional upregulation of these p53 target genes but have no effect on TP53 itself in RS4;11 cells. MD-224 (0.001-1 μM; 24 hours) induces robust apoptosis at ≤10 nM in a dose-dependent manner upon a 24 hours treatment. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: RS4;11 cells Concentration: 1 nM; 3 nM; 10 nM; 30 nM Incubation Time: 2 hours Result: Decreased MDM2 protein and accumulated of p53 protein. RT-PCRCell Line: RS4;11 cells Concentration: 30 nM Incubation Time: 6 hours Result: Upregulated p53 target gene expression. Apoptosis AnalysisCell Line: RS4;11 cells Concentration: 0.001 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1 μM Incubation Time: 24 hours Result: Induces robust apoptosis in RS4;11 cells.Form:SolidIC50& Target:MDM2 1 nM (IC 50 ). Specification: 0.98 Molecular Formula: C48H43Cl2FN6O6 Molecular Weight: 889.8 PubChem CID: 131986956 Isomeric SMILES: C1CCC2(CC1)[C@@]3([C@H]([C@@H](N2)C(=O)NC4=CC=C(C=C4)C(=O)NCCCC#CC5=C6CN(C(=O)C6=CC=C5)C7CCC(=O)NC7=O)C8=C(C(=CC=C8)Cl)F)C9=C(C=C(C=C9)Cl)NC3=O