Dot1L-IN-1 TFA is a highly potent and selective Dot1L inhibitor with a Ki of 2 pM and an IC50 of <0.1 nM. Dot1L-IN-1 TFA potently suppresses H3K79 dimetlation (IC50=3 nM), as well as the activity of the HoxA9 promoter (IC50=17 nM) in HeLa and Molm-13 cells, respectively[1].
Dot1L-IN-1 (analogue 7) TFA effectively inhibits proliferation of the human MLL-rearranged leukemia cell line MV4-11 carrying the oncogenic MLL-AF4 fusion (IC50=5 nM)[1].
[1]. MÖbitz H, et al. Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach. ACS Med Chem Lett. 2017 Feb 14;8(3):338-343.