Unknown

Cmk were tested against the Src-family kinase Fyn, which has a threonine gatekeeper, which in principle should recognize the C-5 aromatic substituent of our inhibitors. At a concentration of 30 nM, cmk had no effect on wild-type (WT) Fyn, whereas it rapidly inactivated an engineered Fyn construct containing a cysteine in place of Val285. In the presence of 1 mM ATP, WT Fyn was relatively resistant to cmk, with IC50 values of 18 mM, respectively. In contrast, 100 nM cmk inactivated Val285Cys Fyn in less than 5 min under these conditions.