EC 144, a second-generation selective inhibitor of Hsp90 (heat shock protein 90), inhibits tumor growth with an IC50= 1.1 nM for Hsp90α and an EC50 = 14 nM for degradation of Her-2 in MCF-7 cells.

EC 144 is a synthetic Hsp90 inhibitor, blocks LPS-induced TLR4 signaling in RAW 264.7 cells by inhibiting activation of ERK1/2, MEK1/2, JNK, and p38 MAPK but not NF-κB. EC 144 inhibited CD4(+) T cell proliferation in both mouse and human mixed lymphocyte reactions (MLRs), indicating an immunosuppressive effect on adaptive immune activation. [1]

In mice treated with EC 144, peritoneal CD11b(+) exudate cells showed reduced phosphorylation of tumor progression locus 2, MEK1/2, and ERK1/2 upon LPS challenge. This corresponded with resistance to LPS-induced systemic inflammation and suppressed TNF-α release. In a mouse collagen-induced arthritis model, EC 144 suppressed arthritis development, correlated with a reduction in antigen-specific antibody production and impaired activation of antigen-specific CD4(+) T cells. [1]