SPL-410 (SPL410) is a highly potent, selective, orally active inhibitor SPPL2a (Signal Peptide Peptidase Like 2a) with IC50 of 9 nM.
Both human and mouse SPPL2a was inhibited with high potency (IC50 of 0.004 μM and 0.005 μM) in high content imaging assay (HCA).
SPL-410 is selective against closely related human aspartyl proteases such as SPP (0.65 μM) and γ-secretase (1.3 μM) as well as SPPL2b (0.27 μM in HCA)
SPL-410 inhibited the processing of the endogenous substrate CD74/p8 NTF in IC50 of 0.15 μM in the mouse B cell line A20.
SPL-410 caused accumulation of CD74/p8 NTF (10 mg/kg single p.o. dose) in mice, achieved a higher efficacy than LY-411575.
