Uses
1-[[3-Fluoro-4-[5-[(2-fluorophenyl)methyl]-2-benzothiazolyl]phenyl]methyl]-3-azetidinecarboxylic Acid is a potent Sphingosine-1-Phosphate Receptor 1 (S1P1) agonist with minimal activity at S1P3. It has been shown to attenuate DTH response to antigen challenge while significantly reducing blood lymphocyte counts.
Biological Activity
ec50: 0.042 μm for hs1p1tc-sp 14 is an agonist of sphingosine-1-phosphate receptor 1 (s1p1).studies have revealed that the lysophospholipid sphingosine-1-phosphate (s1p1) is a pleiotropic modulator of diverse cellular processes. such effects are reported to be mediated by the interactions of s1p with a set of paralogous g proteincoupled receptors, which are widely expressed in the immune, central nervous and cardiovascular systems.
in vitro
as a small lipophilic substituent proved equally effective to a larger substituent in reducing s1p3 activity, tc-sp 14 was screened. tc-sp 14 was found to be a potent s1p1 agonist (ec50 = 0.042 μm) with reduced activity for s1p3 (ec50 = 3.47 μm) [1].
in vivo
in lewis rats, tc-sp 14 produced a dose-dependent reduction in circulating blood lymphocytes, which was consistent with s1p1 agonism. moreover, statistical significance was shown at a dose of 0.3 mg/kg, and the dose fo 3.0 mg/kg led to near maximal lymphopenia. tc-sp 14 was subsequently investigated in a dth antigen challenge model. results showed a statistically significant reduction in ear swelling at doses of 0.3 mg/kg and higher. in addition, reduced ear swelling was found to closely track circulating lymphocyte counts [1].
IC 50
S1PR1: 0.042 μM (EC50); S1PR3: 3.47 μM (EC50)
References
[1] lanman ba,cee vj,cheruku sr et al. discovery of a potent, s1p3-sparing benzothiazole agonist of sphingosine-1-phosphate receptor 1 (s1p1). acs med chem lett.2010 nov 9;2(2):102-6.
