GSK143 is a potent orally active and highly selective inhibitor of spleen tyrosine kinase (SYK) with a pIC 50 of 7.5. Furthermore, GSK143 effectively inhibits phosphorylated Erk (pErk) with a pIC 50 value of 7.1. In addition, GSK143 exhibits promising anti-inflammatory properties by reducing inflammation and impeding the recruitment of immune cells in the intestinal muscularis of mice.

GSK143 (compound 20) effectively inhibits several enzymes and receptors, displaying inhibitory activities against ZAP-70 (pIC 50 =4.7), LCK (pIC 50 =5.3), LYN (pIC 50 =5.4), JAK1/2/3 (pIC 50 =5.8/5.8/5.7), Aurora B (pIC 50 =4.8), hWB (pIC 50 =6.6), and hERG (pIC 50 =4.7)[1]. When tested on chronic lymphocytic leukemia (CLL) cells with concentrations ranging from 10-10000 nM over a period of every 24 hours for three days, GSK143 achieves an IC 50 of 323 nM, demonstrating its efficacy in reducing cell viability[2]. Furthermore, exposure to GSK143 (1 μM; 30 mins) interrupts early signaling pathways by hindering SYK phosphorylation and calcium flux[2], and its application (0.1-10 μM; for 30 min) diminishes cytokine expression in bone marrow-derived macrophages in a concentration-dependent manner[3].

GSK143, administered orally at dosages ranging from 0.1 to 10 mg/kg 1.5 hours prior to intestinal manipulation, significantly reduces inflammation and prevents the recruitment of immune cells in the intestinal muscularis of mice, demonstrating its anti-inflammatory capabilities. When administered orally at dosages of 3, 10, 30, and 100 mg/kg 1 hour before an ovalbumin challenge, GSK143 diminishes the severity of the cutaneous reverse passive Arthus reaction in a dose-dependent manner, with reductions of approximately 50% and 70% observed at doses of 10 mg/kg and 30 mg/kg, respectively. Pharmacokinetic analysis in rats reveals that GSK143, at an intravenous dosage of 1 mg/kg and an oral dosage of 3 mg/kg, has a half-life (T 1/2) of 4.2 hours, low clearance (16 mL/min/kg), a bioavailability of 30%, and a steady-state volume of distribution (Vss) of 4.1 L/kg. The studies were conducted in wild-type C57NL/BL6 mice aged 10-12 weeks and male CD rats weighing 175-200 g.