TC-SP 14

TC-SP 14 (compound 14) is an orally active and potent S1P1 agonist (EC50 = 0.042 μM) with minimal activity at S1P3 (EC50 = 3.47 μM). TC-SP 14 significantly reduces blood lymphocyte counts and attenuates a delayed type hypersensitivity (DTH) response to antigen challenge[1].

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

Research Areas >> Inflammation/Immunology

S1PR1:0.042 μM (EC50)

S1PR3:3.47 μM (EC50)

TC-SP 14 (compound 14) neither inhibits nor induces human cytochrome P450 enzymes, is nonmutagenic, and dose not significantly inhibit the hERG channel[1].

TC-SP 14 (compound 14) (0-3 mg/kg, Orally, once) produces a dose-dependent reduction in circulating blood lymphocytes 24 h postdose[1]. TC-SP 14 (0-3 mg/kg, Orally, daily for 10 days) significant reduces ovalbumin (OVA)-induced ear swelling[1]. TC-SP 14 (2-15 mg/kg, IV or PO, once) possesses acceptable characteristics[1]. Pharmacokinetic Parameters of TC-SP 14 in female Sprague-Dawley rats and male Cynomolgus [1]. species rat NHP CL (L/h/kg) 0.33 0.50 Vss (L/kg) 3.3 1.6 T1/2 (h) 7.5 35.2 MRT (h) 10 3.3 % F 68 23 Animal Model: Lewis rats (female, n = 5/group)[1] Dosage: 0.3, 1.0, and 3.0 mg/kg Administration: Orally, once Result: Produced a dose-dependent reduction in circulating blood lymphocytes 24 h postdose, resulted in near maximal lymphopenia at 3.0 mg/kg (74% reduction in lymphocytes vs vehicle). Animal Model: OVA-immunized Lewis rats (female, n = 8/group)[1] Dosage: 0.1, 0.3, 1.0, and 3.0 mg/kg Administration: Orally, daily for 10 days Result: Significant reduced OVA-induced ear swelling at doses of 0.3 mg/kg and higher. Animal Model: Female Sprague-Dawley rats, Male Cynomolgus (NHP (nonhuman primates)) (n=3/group)[1] Dosage: 2 (IV, rat), 4 (IV, NHP), 10 (PO, NHP), 15 mg/kg (PO, rat) Administration: IV, PO, once (Pharmacokinetic Analysis) Result: Possessed acceptable characteristics, demonstrated low clearance, moderate steady state volumes of distribution, moderate-to-long mean residence times, and acceptable oral bioavailability.

[1]. Lanman BA, 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.