SLF1081851

SLF1081851 (16 d) is an effective Sphingolipid Transporter 2 (Spns2) (S1P transporter) inhibitor with an IC50 value of 1.93 μM (S1P), SLF1081851 inhibits SphK2 with an IC50 value of ≈ 30 μM (SphK2), and is at least 15-fold more selective for SphK2 than SphK1. SLF1081851 has the potential to investigate Spns2 biology and can be used for autoimmune encephalomyelitis (EAE) research[1].

Signaling Pathways >> GPCR/G Protein >> LPL Receptor

Research Areas >> Inflammation/Immunology

IC50: 1.93 μM (SIP), ≈ 30 μM (SphK2)[1].

SLF1081851 (C57BL/6j strain mice or Sprague-Dawley strain rats; 10 or20 mg/kg; i.p., 4 h postdose) significantly inhibits circulating lymphocytes and plasma S1P, recapitulates the genetic phenotype of Spns2 null mice[1]. Animal Model: Mice (C57BL/6j strain), rats (Sprague-Dawley strain)[1]. Dosage: 10, 20 mg/kg. Administration: I.p., blood was drawn 4 h postdose. Result: Inhibited circulating lymphocytes and plasma S1P [1]. Animal Model: 4 week old male rats[1]. Dosage: 10 mg/kg. Administration: I.p. (Pharmacokinetic Analysis). Result: Reached a maximum concentration of 5 μM in blood at 2 h with drug levels sustained at ≥ 2 μM for at least 24 h, proved a half-life of over 8 h in rats. The appearance of SPNS2-IN-1 in circulation correlated with a maximal decrease in lymphocyte count at 4 h (25% lower compared to time = 0).

[1]. Russell Fritzemeier, et al. Discovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors. J Med Chem. 2022 Jun 9;65(11):7656-7681