Uses
A 419259 Trihydrochloride is the hydrochloride form of A 419259 which is a Src kinase inhibitor and can be used in treatment of chronic myelogenous leukemia, lymphangioleiomyomatosis and tuberous sclerosis.
Biological Activity
a 419259 trihydrochloride is an orally available inhibitor of lck with ic50 value of 15 nm [1].lck is a src family tyrosine kinase. inhibition of this enzyme results in a prevention of t-cell activation and provides an application for treating t-cell dependent processes such as autoimmune and inflammatory diseases. a 419259 trihydrochloride is screened out by its potent inhibitory activity against the recombinant lck (64–509) with ic50 value of 15nm. it is also a selective inhibitor. it shows inactive against a panel of other kinases including cmet, igfr, pkc and pdgfr. besides that, a 419259 trihydrochloride is found to inhibit the production of il-2 with ic50 value of 25nm in jurkat cells. moreover, administration of a 419259 trihydrochloride reduces il-2 production in mice with ed50 value of 2.5 mg/kg. a 419259 trihydrochloride also has efficacy of the antigen specific t-cell immune response. administration of this compound inhibits ifn-γ production during the in vivo priming phase [1].
References
[1] calderwood d j, johnston d n, munschauer r, et al. pyrrolo [2, 3-d] pyrimidines containing diverse n-7 substituents as potent inhibitors of lck. bioorganic & medicinal chemistry letters, 2002, 12(12): 1683-1686.
