SEL24-B489 is a highly effective and orally bioavailable compound that acts as a robust, type I inhibitor of both PIM and FLT3-ITD. It exhibits exceptional binding affinity with K d values of 2 nM for PIM1, 2 nM for PIM2, and 3 nM for PIM3.

Pim1:2 nM (Kd), Pim3:3 nM (Kd), Pim2:2 nM (Kd)

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 (S 235/236 ), but has little effect on PI3K/mTOR signaling[1]. SEL24-B489 inhibits STAT5 (Ser 726 ) and reduced expression of MCL1, whereas none of the selective inhibitors altered c-MYC abundance or induced PARP cleavage[1]. Cell Viability Assay[1]Cell Line: AZD1208, AC220 and AraC in AML cell lines. Concentration: 0-10 μM. Incubation Time: 72 h. Result: Decreased viability.

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]. Animal Model: SCID/beige mice bearing MV-4-11 tumors (FLT3-ITD+)[1]. Dosage: 50, 75 and 100 mg/kg. Administration: Orally, twice daily. Result: Marked dose – dependent tumor reduction (67%, 74% and 82% tumor growth inhibition (TGI) for 50, 75 and 100 mg/kg daily doses, respectively).