| 描述 | TC-SP 14, also known as compound 14, is a highly active and potent S1P1 agonist with oral bioavailability. It exhibits an EC50 value of 0.042 μM, indicating its strong binding affinity to the S1P1 receptor. Notably, its interaction with the S1P3 receptor is minimal, as evidenced by an EC50 value of 3.47 μM. TC-SP 14 demonstrates significant pharmacological effects, including a marked reduction in blood lymphocyte counts and the attenuation of delayed type hypersensitivity response to antigen challenge [1]. |
| 體內(nèi)活性 | TC-SP 14 (compound 14) (0-3 mg/kg, Orally, once) produces a dose-dependent reduction in circulating blood lymphocytes 24 h after dosing [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 T 1/2 (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. |