GSK143 dihydrochloride is a highly selective, orally active inhibitor of spleen tyrosine kinase (SYK), exhibiting a pIC 50 value of 7.5. It effectively inhibits phosphorylated Erk (pErk) with a pIC 50 value of 7.1. The compound demonstrates anti-inflammatory properties and hinders the recruitment of immune cells in the intestinal muscularis of mice.

GSK143 dihydrochloride (compound 20) effectively inhibits a range of kinases including 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). When administered at concentrations ranging from 10 to 10,000 nM every 24 hours over a three-day period, it exhibits an IC 50 of 323 nM in chronic lymphocytic leukaemia (CLL) cells. Additionally, a one-time dose of 1 μM for 30 minutes interrupts early signaling mechanisms, notably SYK phosphorylation and calcium flux. Furthermore, dosages between 0.1 to 10 μM for 30 minutes conditionally lessen cytokine production in bone marrow-derived macrophages. This compound's ability to selectively inhibit these targets, particularly its efficacy at a specific concentration in CLL cells with an IC 50 of 323 nM, underscores its potential for therapeutic applications, demonstrating varied impacts on cellular processes and signaling pathways critical in disease pathogenesis.

GSK143 reduces inflammation and prevents immune cell recruitment in the intestinal muscularis of wild type C57NL/BL6 mice (0.1-10 mg/kg orally, 1.5 hours before intestinal manipulation)[3], and decreases 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, in male CD rats (3, 10, 30, 100 mg/kg orally, 1 hour before ovalbumin challenge)[2]. In pharmacokinetic analysis, GSK143 (1 mg/kg IV; 3 mg/kg PO) exhibits a T 1/2 of 4.2 hours, low clearance (16 mL/min/kg), moderate bioavailability (30%), and a V ss of 4.1 L/kg in male CD rats[1].