RETRACTED: A novel class of specific Hsp90 small molecule inhibitors demonstrate in vitro and in vivo anti-tumor activity in human melanoma cells (Retracted article. See vol. 422, pg. 132, 2018)

Hsp90 is required for conformational maturation and stability of numerous key signaling proteins (clients) involved in cell proliferation and transformation Here we describe two novel Hsp90 inhibitors PF-4470296 and PF-3823863 demonstrate a differential sensitivity in B-Raf mutant (V600E) versus wild-type protein degradation These two inhibitors inhibit proliferation and anchorage-independent growth and abolish in vivo xenograft tumor growth in melanoma cells regardless of B-Raf mutation status Mutant B-Raf protein and other Hsp90 clients such as cMet ErbB2 C-Raf and ART are degraded in cells and xenograft tumors Our results indicate that Hsp90 inhibitors induce anti-tumor activity in melanoma cells and are likely to show therapeutic benefit in melanoma patients by collaboratively targeting multiple pathways (c) 2010 Elsevier Ireland Ltd All rights reserved