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, MV4-11 cells, SEL24-B489 prompts a dose-dependent disruption of the cell cycle, notably depleting the S phase, leading to PARP cleavage and apoptosis[1]. Moreover, SEL24-B489 significantly inhibits S6 (S 235/236) while minimally affecting PI3K/mTOR signaling[1]. It also suppresses STAT5 (Ser 726) and reduces MCL1 expression without altering c-MYC levels or prompting PARP cleavage, unlike selective inhibitors[1]. In a Cell Viability Assay[1] using AML cell lines with AZD1208, AC220, and AraC at 0-10 μM concentrations over 72 hours, a noticeable decline in cell viability was observed.

SEL24-B489, when administered orally at doses ranging from 25-100 mg/kg, demonstrated effectiveness against Acute Myeloid Leukemia (AML) in vivo[1]. Additionally, it effectively induced apoptosis in Diffuse Large B-Cell Lymphoma (DLBCL) cell lines at low/sub-micromolar concentrations and showed efficacy in a xenograft model[2]. In an animal study using SCID/beige mice implanted with MV-4-11 tumors (FLT3-ITD+), doses of 50, 75, and 100 mg/kg given orally twice daily resulted in significant, dose-dependent tumor reduction, achieving 67%, 74%, and 82% tumor growth inhibition (TGI) for the respective daily doses[1].