Stemcell, 100-1655, EPZ004777 (Formate)

Induce anti-tumor effects in a variety of cancer cells with EPZ004777 (Formate), a potent inhibitor of the disruptor of telomeric silencing 1 (DOT1)-like histone lysine methyltransferase (DOT1L; IC50 = 400 pM). Through DOT1L inhibition, EPZ004777 (Formate) prevents DOT1L-mediated methylation of lysine 79 of histone 3 (H3K79; Daigle et al. Cancer Cell, 2011), which is known to impact telomeric silencing, transcriptional regulation, DNA-damage repair, and cell cycle progression (Nguyen & Zhang. Genes Dev, 2011). Dysregulation of DOTL1-mediated H3K79 methylation is involved in the development of mixed-lineage leukemia (MLL) and the pathophysiology of other cancers (McLean et al. Leukemia, 2014).

EPZ004777 (Formate) has been used for:

CANCER RESEARCH

· Reduce cell viability and colony formation in human prostate cancer cell lines and patient-derived xenograft model (Vatapalli et al. Nat Commun, 2020).

· Inhibit cell growth and upregulate pro-apoptotic genes in a mouse xenograft model of ovarian cancer and human ovarian cancer cell lines (Chava et al. Oncogenesis, 2021).

· Reduce mouse pancreatic and colon cancer cell viability and colony formation and reduce tumor growth in a mouse xenograft model (Zhou et al. Mol Oncol, 2019).

· Induce apoptosis, cell-cycle arrest, and terminal differentiation in human acute myeloid leukemia cells and suppress leukemic tumor growth in a mouse xenograft model (Rau et al. Blood, 2016).