SPL-707 is an orally active, selective signal peptide peptidase-like 2a (SPPL2a) inhibitor with an IC50 of 77 nM for hSPPL2a. SPL-707 inhibits γ-secretase (IC50=6.1 μM) and SPP (IC50=3.7 μM). SPL-707 has the potential for autoimmune diseases research by targeting B cells and dendritic cells.
SPL-707 (Compound 40) inhibits mouse SPPL2a (IC50=0.18 μM), rat SPPL2a (IC50=0.056 μM) and human SPPL2a (IC50=0.16 μM), human SPPL2b (IC50=0.43 μM) by a high content imaging assay (HCA).
体内研究
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.
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.
分子式
C27H28FN5O4
分子量
505.54
CAS号
2195361-33-0
运输条件
Room temperature in continental US; may vary elsewhere.