Lck is a src-family tyrosine kinase that predominantly expressed in T lymphocytes. The inhibition of lck activity prevents the activation of T cells, which might be used for the treatment of T-cell-dependent diseases. RK 24466 is a pyrrolopyrimidine that inhibits the activity of two forms of lck kinase, lck (64-509) and lckcd, with IC50 values of <1 nM and 2 nM, respectively. It also blocks kinases scr, kdr, and tie-2 with IC50 values of 0.07, 1.57, and 1.98 µM, respectively. RK 24466 showed much less inhibitory effect on the activities of EGFR, Zap70, PKC, and CDC2/CyB with IC50s values of 3.2 µM, >50 µM, >33 µM, and >50 µM, respectively[1]. The i.p. administration of RK 24466 at low doses (ED50 = 4 mg/kg) inhibited T-cell receptor-stimulated IL-2 production in mice, while the efficacy was remarkably decreased after the oral administration (ED50 = 25 mg/kg)[2].
作用机制
RK 24466 is a potent and selective inhibitor of lck kinase. The hydrophobic pocket in lck (64-509) is occupied by the phenoxyphenyl moiety of RK 24466, resulting in an increased potency against lck (64-509).
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