YH239-EE is a potent antagonist of p53-MDM2 [1].
p53 is a transcription factor and functions as a tumor suppressor. MDM2 is a negative regulator of p53. The interaction of p53 and MDM2 has emerged as a novel target for anticancer drugs [1].
YH239-EE is a potent p53-MDM2 antagonist. In OCI-AML-3 cells, YH239-EE potently inhibited cell proliferation. In AML cell lines, YH239-EE induced a cell cycle arrest and cell accumulation in the sub-G1 phase. YH239-EE induced apoptosis by 11.8-fold, 5.6-fold and 13.1-fold in OCI-AML-3, MOLM-13 and NB4 AML cell lines, respectively. In MOLM-13 cells, YH239 exhibited almost no apoptotic effect. However, YH239-EE significantly induced apoptosis. In MOLM-13 cells, (+)-YH239-EE and (−)-YH239-EE inhibited metabolic activity with EC50 values of 7.5 μM and 25.2 μM and induced apoptosis with 13.7% and 51.5% viable cells, respectively. (+)-YH239-EE (20 μM) induced p53 and significantly activated caspase 3 and 7 [1].
Reference:
[1]. Huang Y, Wolf S, Beck B, et al. Discovery of highly potent p53-MDM2 antagonists and structural basis for anti-acute myeloid leukemia activities. ACS Chem Biol, 2014, 9(3): 802-811.