背景介绍 EPZ004777 selectively inhibits cellular H3K79 methylation and inhibits expression of key MLL fusion target genes. EPZ004777 produces potent antitumor efficacy, and significantly increases median survival in a mouse xenograft model of MLL leukemia. Following DOT1L inhibition, EPZ004777 selectively inhibits proliferation of MLL-rearranged cell lines and MLL-AF9-transformed murine hematopoietic cells. In addition, EPZ004777 also induces differentiation and apoptosis in MLL-rearranged cells. DOT1L inhibition by EPZ004777 results in significantly decreased proliferation, decreased expression of MLL-AF6 target genes, and cell cycle arrest of MLL-AF6-transformed cells. EPZ004777 has also been found to selectively inhibit the proliferation of MLL-AF10 and CALM-AF10 transformed cells in a dose dependent manner (IC50: 0.1 µM to 1 µM), in which the mRNA expression levels of two hallmark leukemogenic genes (Hoxa9 and Meis1) are suppressed by EPZ004777 in a concentration dependent manner. 产品介绍 EPZ004777 is a potent, selective DOT1L inhibitor with IC50 of 400 pM. EPZ004777 selectively kills a variety of MLL-rearranged leukemia cells, including an MLL-AF4 leukemia cell line MV4-11 and an MLL-AF9 leukemia cell line MOLM13.