GSK143

GSK143 is an orally active and highly selective spleen tyrosine kinase (SYK) inhibitor with a pIC₅₀ of 7.5. GSK143 inhibits phosphorylated Erk (pErk: pIC₅₀=7.1)^[1]. GSK143 reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis in mice^[2][3]. IC50 & Target: pIC50: 7.5 (SYK) and 7.1 (pErk)^[1] In Vitro: GSK143 (compound 20) inhibits ZAP-70 (pIC₅₀=4.7), LCK (pIC₅₀=5.3), LYN (pIC₅₀=5.4), JAK1/2/3 (pIC₅₀=5.8/5.8/5.7), Aurora B (pIC₅₀=4.8), hWB (pIC₅₀=6.6), hERG (pIC₅₀=4.7)^[1].
GSK143 (10-10000 nM; every 24 h for 3 days) has an IC₅₀ of 323 nM in CLL cells. GSK 143 (1 μM; 30 mins) abrogates early signalling events including SYK phosphorylation and calcium flux^[2].
GSK143 (0.1-10 μM; for 30 min) reduces cytokine expression in bone marrow derived macrophages in a concentration-dependent manner^[3].
In Vivo: GSK143 (0.1-10 mg/kg; orally; 1.5 hours) reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis of 1 mg/kg^[3].
GSK143 (3, 10, 30, 100 mg/kg; oral; 1 hour before ovalbumin challenge) reduces the cutaneous reverse passive Arthus reaction in a dose dependent manner by approximately 50% and 70% at 10 mg/kg and 30 mg/kg, respectively^[2].
GSK143 (iv of 1 mg/kg; po of 3 mg/kg) has a T_1/2 of 4.2 hours, low clearance (16 mL/min/kg), moderate bioavailability of 30% and a V_ss of 4.1 L/kg in rats^[1].