SEL24-B489 is a potent, type I, orally active, dual PIM and FLT3-ITD inhibitor, with Kd values of 2 nM for PIM1, 2 nM for PIM2 and 3 nM for PIM3, respectively[1].
In MOLM-13 and to a lesser extent in MV4-11 cells, a dose-dependent disruption of cell cycle with especially pronounced depletion of the S phase after treatment with SEL24-B489, accompanied by PARP cleavage and apoptosis was observed[1].SEL24-B489 causes a profound inhibition of S6 (S235/236), but has little effect on PI3K/mTOR signaling[1].SEL24-B489 inhibits STAT5 (Ser726) and reduced expression of MCL1, whereas none of the selective inhibitors altered c-MYC abundance or induced PARP cleavage[1].
SEL24-B489 (25-100 mg/kg, orally) exhibited activity in AML in vivo models[1].SEL24-B489 induces apoptosis of DLBCL cell lines in low/sub-micromolar concentrations and exhibits activity in a xenograft model[2].
[1]. Wojciech Czardybon, A novel, dual pan-PIM/FLT3 inhibitor SEL24 exhibits broad therapeutic potential in acute myeloid leukemia. Oncotarget. 2018 Mar 30;9(24):16917-16931.
[2]. Ewa Jablonska, et al. A Novel Pan-PIM Kinase Inhibitor, SEL24-B489, Induces Apoptosis and Inhibits Proliferation of Diffuse Large B-Cell Lymphoma Cells through Inhibition of Protein Translation and Attenuation of Myc and NFkB Activity. Blood (2015) 126 (23): 706.