Lck Inhibitor

Lck Inhibitor is a potent, orally active Lck (lymphocyte specific kinase) inhibitor with IC₅₀s of 7, 2.1, 4.2 and 200 nM for Lck, Lyn, Src and Syk kinases, respectively. Lck Inhibitor shows >1000-fold selectivity for Lck over MAPK, CDK and RSK family representatives. Lck Inhibitor inhibits T cell proliferation and in vivo models of arthritis^[1]. In Vitro: Lck Inhibitor (compound 25) exhibits good potency in the T-cell receptor-induced IL-2 secretion assay (IL-2, IC₅₀=0.46 μM) and also inhibits subsequent T-cell proliferation (T-cell prolif, IC₅₀=0.53 μM) in the same human T-cells. Lck Inhibitor also inhibits a human mixed lymphocyte reaction (huMLR) with a 10-fold increase in potency as compared to the other invitro cell assays utilizing purified human cells. Lck Inhibitor also displays inhibition of a mechanism-based biochemical cell assay probing Lck-dependent TCR-chain phosphorylation (TCR-chain). Lck Inhibitor shows a 10-fold reduction in potency when IL-2 is induced in a receptor-independent fashion by stimulating with phorbo lester and calcium ionophore (PMA/iono). Lck Inhibitor exhibits a similar level of potency when tested in a general proliferation assay using the human T-cell line, Jurkat (JKT)^[1]. In Vivo: Lck Inhibitor (0-60 mg/kg; p.o.; once daily; from day 9 today 17) shows a dose-dependent inhibition of arthritis^[1].
Lck Inhibitor (p.o.; 5 mg/kg) treatment shows the C_max, AUC_0-∞, t_max and F% are 82 ng/mL, 862 ng h/mL, and 17%, respectively^[1].