EC50: 0.042 μM for hS1P1
TC-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].
Clinical trial: N/A
Reference:
[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.