S32826 is a highly potent inhibitor of autotaxin, exhibiting an IC50 value of 8.8 nM. It displays comparable inhibitory properties towards various autotaxin isoforms, including α, β, and γ. Furthermore, S32826 effectively inhibits the release of LPA from adipocytes.

ATX:8.8 nM (IC50)

S32826, at concentrations ranging from 0.001 to 10 μM over a period of 10 days, dose-dependently reduces lyso-phosphatidic acid (LPA) secretion by 3T3-F442A adipocytes, with an IC 50 value of 90 nM and achieving a peak suppression of 80% at 500 nM[1]. Additionally, at a concentration of 1 μM for 24 hours, S32826 effectively blocks the Dexamethasone-induced surge in autotaxin (ATX) mRNA levels and lysophospholipase D (lysoPLD) activity in the conditioned media of HTM cells. It also prevents Dexamethasone-triggered phosphorylation of myosin light chain (MLC) and cofilin, as well as the mRNA overexpression of COL1A1 and COL4A1, alongside inhibiting the expression of α-SMA, fibronectin, and collagen-1 in HTM cells[2].

Topical application of S32826 at concentrations ranging from 2 to 10 mM for 2 hours to 5 days leads to a dose- and time-dependent reduction in intraocular pressure (IOP) in rabbits[2]. A single intracameral injection of approximately 2 μM S32826 also decreases IOP in rabbits, maintaining the ocular hypotensive effect for over 48 hours[2]. However, when administered orally (p.o.), intraperitoneally (i.p.), subcutaneously (s.c.), or intravenously (i.v.) at a dose of 10 mg/kg, S32826 demonstrates poor in vivo stability and/or bioavailability[1].