RK-24466 (KIN 001-51)

Lymphocyte-speci?c protein tyrosine kinase (LCK) is a member of the Src-family of non-receptor protein tyrosine kinases and plays a critical role in the initial steps of T cell receptor signaling that trigger the production of cytokines.¹ LCK inhibitor is a pyrrolopyrimidine that blocks the activity of two forms of LCK kinase, LCK (64-509) and LCKCD, with IC₅₀ values of <1 and 2 nM, respectively.^2,3 It inhibits the related kinases Src, Kdr, and Tie-2 with much weaker potency (IC₅₀s = 70 nM, 1.57, and 1.98 ?M, respectively) and only minimally inhibits the activities of EGFR, PKC, CDC2/B and ZAP-70 (IC₅₀s = 3.2, >33, >50, and >50 ?M, respectively).^2,3 This compound has been shown to inhibit T cell receptor-stimulated IL-2 production in mice (ED₅₀s = 4 and 25 mg/kg when administered either i.p. or orally).^2,4

1.Khatik, R., and Pathak, A.K.Lck inhibitors and its analogues: A reviewDer Pharma Chemica3(2)310-320(2011) 2.Burchat, A.F., Calderwood, D.J., Hirst, G.C., et al.Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck IIBioorg. Med. Chem. Lett.10(19)2171-2174(2000) 3.Arnold, L.D., Calderwood, D.J., Dixon, R.W., et al.Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck IBioorg. Med. Chem. Lett.10(19)2167-2170(2000) 4.Calderwood, D.J., Johnston, D.N., Munschauer, R., et al.Pyrrolo[2,3-d]pyrimidines containing diverse N-7 substituents as potent inhibitors of LckBioorg. Med. Chem. Lett.12(12)1683-1686(2002)