| Description |
SLF1081851 (TFA) is a Spns2 inhibitor, inhibits S1P release (IC50=1.93 μM). SLF1081851 (TFA) plays a key role in development and immune system[1][2].
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| Related Catalog |
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| Target |
Spns2 (spinster homologue 2)[1]
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| In Vitro |
Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule, and Spns2 exerts the functions to maintain lymph S1P[1]. SLF1081851 (TFA) (compound 16d) (0-5 μM; 18-20 h) inhibits S1P release with an IC50 value of 1.93 μM in Hela cells[1]. SLF1081851 (TFA) (0-30 μM; 20 min) inhibits mSphK1 (recombinant mouse SphK) (10 μM) and mSphK2 (5 μM) in a dose-dependent manner and suggests at least 15-fold selectivity (SphK1 IC50≥30 μM; SphK2 IC50≈30 μM)[1].
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| In Vivo |
SLF1081851 (TFA) (20 mg/kg; i.p., 4 h postdose) significantly inhibits circulating lymphocytes and plasma S1P, and recapitulates the genetic phenotype of Spns2 null mice[1]. Animal Model: C57BL/6 mice[1] Dosage: 20 mg/kg Administration: Intraperitoneal injection; blood was drawn 4 h postdose Result: Significantly decreased circulating lymphocyte count and plasma S1P concentration. Animal Model: SpragueDawley mice (4-week-old)[1] Dosage: 10 mg/kg Administration: Intraperitoneal injection; single dose; measured at 0, 0.5, 1, 2, 4, 6, and 24 h postdose 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).
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| References |
[1]. Fritzemeier R, et al. Discovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors. J Med Chem. 2022 Jun 9;65(11):7656-7681. [2]. Lynch Kevin R, et al. Preparation of oxadiazoles as inhibitors of spinster homolog 2 (SPNS2) for use in therapy: World Intellectual Property Organization, WO2022056042[P]. 2022-03-17.
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