SPL-707_product_DataBase

Bioactivity

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[1].

Target

IC50: 77 nM (SPPL2a), 6.1 μM (γ-secretase) and 3.7 μM (SPP)

Invitro

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)[1].

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[1]. 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[1]. 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[1]. Animal Model:

Name

SPL-707

CAS

2195361-33-0

Formula

C27H28FN5O4

Molar Mass

505.54

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Velcicky J, et al. Discovery of the First Potent, Selective, and Orally Bioavailable Signal Peptide Peptidase-Like 2a (SPPL2a) Inhibitor Displaying Pronounced Immunomodulatory Effects In Vivo. J Med Chem. 2018 Feb 8;61(3):865-880.

PeptideDB

SPL-707

CAS: 2195361-33-0 F: C27H28FN5O4 W: 505.54