SPL-707 is an orally active, selective signal peptide peptidase-like 2a (SPPL2a) inhibitor with an IC 50 of 77 nM for hSPPL2a. SPL-707 inhibits γ-secretase ( IC 50 =6.1 μM) and SPP ( IC 50 =3.7 μM). SPL-707 has the potential for autoimmune diseases research by targeting B cells and dendritic cells In Vitro SPL-707 (Compound 40) inhibits mouse SPPL2a (IC 50 =0.18 μM), rat SPPL2a (IC 50 =0.056 μM) and human SPPL2a (IC 50 =0.16 μM), human SPPL2b (IC 50 =0.43 μM) by a high content imaging assay (HCA). MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo SPL-707 (Compound 40; 3-30 mg/kg; orally; b.i.d.; for 11 days) leads to a reduction in B cells and myeloid dendritic cells without affecting γ-secretase activity . SPL-707 (3 mg/kg of po and 1 mg/kg of iv) has a CL of 6 mL/min•kg, and an AUC of 8787 h•nM . SPL-707 (1, 3 mg/kg; b.i.d.; first dose at 0 h, second dose at 8 h) achieves full inhibition of CD74/p8 processing in spleen in female Lewis rats . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Mice with 5-12 weeks of age Dosage: 3, 10, and 30 mg/kg Administration: Orally; b.i.d. (with 8 and 16 h dosing intervals); for 11 days Result: Led to a reduction in B cells and myeloid dendritic cells without affecting γ-secretase activity. Animal Model: Female Sprague−Dawley rat Dosage: 3 mg/kg of po and 1 mg/kg of iv (Pharmacokinetic Analysis) Administration: PO or IV Result: Had a CL of 6 mL/min•kg, and an AUC of 8787 h•nM. Form:Solid IC50& Target:IC50: 77 nM (SPPL2a), 6.1 μM (γ-secretase) and 3.7 μM (SPP)