RK‐682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at G1phase

Abstract

A specific inhibitor of protein tyrosine phosphatase (PTPase), RK‐682 (3‐hexadecanoyl‐5‐hydroxymethyl‐tetronic acid) was isolated from microbial metabolites. In vitro, RK‐682 inhibited dephosphorylation activity of CD45 and VHR with IC₅₀ 54 and 2.0 μM, respectively. In situ, sodium orthovanadate and RK‐682 enhanced the phosphotyrosine level of Ball‐1 cells, a human B cell leukemia, but not the phosphoserine/threonine level. The PTPase inhibitors, however, had the different arrest point on the cell cycle progression. Sodium orthovanadate inhibited the cell cycle progression at G₂/M boundary phase, on the other hand, RK‐682 inhibited the G₁/S transition.