MA242

MA242 is a specific dual inhibitor of MDM2 and NFAT1. MA242 directly binds both MDM2 and NFAT1 with high affinity, induces their protein degradation, and inhibits NFAT1-mediated transcription of MDM2. MA242 induces apoptosis in pancreatic cancer cell lines regardless of p53 status^[1]. IC50 & Target: MDM2, NFAT1^[1] In Vitro: MA242 (0.05-5 μM; 72 hours) significantly inhibits pancreatic cancer cell growth, with IC₅₀s ranging from 0.1 to 0.4 μM, regardless of the p53 status of the cells. However, MA242 shows minimal effects on the growth of normal HPDE cells (IC₅₀=5.81 μM), indicating that MA242 has selective effects against cancer cells^[1].
MA242 (0.1-0.5 μM; 24 hours) significantly decreases the MDM2 and NFAT1 protein levels at a low concentration in all three cell lines^[1].
MA242 decreases cell proliferation and induces apoptosis in pancreatic cancer cell lines regardless of p53 status^[1].
MA242 alone or in combination with Gemcitabine inhibits pancreatic tumor growth and metastasis without any host toxicity^[1].
MA242 exerts cytotoxicity against hepatocellular carcinoma (HCC) cells by inhibiting the NFAT1-MDM2 pathway in vitro, independent of p53. MA242 shows selective cytotoxicity against HCC cells, with IC₅₀ values ranging from 0.1-0.31 μM^[2]. In Vivo: MA242 (IP; 2.5, 5, 10 mg/kg) suppresses orthotopic pancreatic tumor growth in vivo, independent of p53^[1].
There were no significant differences in the average body weights between the vehicle- and MA242-treated mice in either of the models, did not have significant host toxicity at these effective doses^[1].