Document Report Card

ID: ALA1773067

Journal: ACS Med Chem Lett

Title: Identification and characterization of novel inhibitors of mPTPB, an essential virulent phosphatase from Mycobacterium tuberculosis.

Authors: Chen L, Zhou B, Zhang S, Wu L, Wang Y, Franzblau SG, Zhang ZY.

Abstract: Mycobacterium protein tyrosine phosphatase B (mPTPB) is an essential virulence factor required for Mycobacterium tuberculosis (Mtb) survival in host macrophages. Consequently, mPTPB represents an exciting new target with a completely novel mechanism of action. We screened a library of 7,500 compounds against mPTPB and identified several 2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide and piperazinyl-thiophenyl-ethyl-oxalamide derivatives as two distinct classes of mPTPB inhibitors. We showed that both classes of inhibitors are capable of blocking the mPTPB-mediated ERK1/2 inactivation. We further demonstrated that both classes of mPTPB inhibitors are effective in inhibiting the growth of Mtb in macrophages. Thus, improvement of the lead compounds may produce a novel class of anti-TB agents.

CiteXplore: 21116447

DOI: 10.1021/ml1001135