PIM1-IN-1 is a potent and highly selective PIM1/3 inhibitor, with IC50s of 7, 5530 and 70 nM for PIM1, PIM2, and PIM3, respectively, inhibits the phosphorylation of BAD, a downstream target of PIM, with an EC50 of 262 nM. PIM1-IN-1 shows no obvious effect on FLT3 or hERG binding. Antiproliferative and anti-cancer activity[1].
PIM1-IN-1 (Compound 42) exhibits antiproliferative activity, with GI50 of 1.48 μM for melanoma cell line SKMEL-19. PIM1-IN-1 has significant synergistic effect combined with different antitumoral agents in different tumor cell lines[1]. PIM1-IN-1 (2.5, 5, or 10 μM, 24 hours) induces apoptosis in SKMEL19 cells[1].
PIM1-IN-1 shows cceptable clearance of 1.26 L/h/kg in BALB-C mice[1].
[1]. Martínez-González S, et al. Discovery of novel triazolo[4,3-b]pyridazin-3-yl-quinoline derivatives as PIM inhibitors. Eur J Med Chem. 2019 Feb 19;168:87-109.
