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].
[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.
