In Vitro: GSK143 dihydrochloride (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). GSK143 dihydrochloride (10-10000 nM; every 24 hours for 3 days) has an IC50 of 323 nM in CLL cells. GSK 143 dihydrochloride (1 μM; 30 mins) abrogates early signalling events including SYK phosphorylation and calcium flux. GSK143 dihydrochloride (0.1-10 μM; for 30 min) reduces cytokine expression in bone marrow derived macrophages in a concentration-dependent manner.
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. 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. GSK143 (iv of 1 mg/kg; po of 3 mg/kg) has a T1/2 of 4.2 hours, low clearance (16 mL/min/kg), moderate bioavailability of 30% and a Vss of 4.1 L/kg in rats.