The novel HSP90 inhibitor, PU-H71, suppresses glial cell activation but weakly affects clinical signs of EAE

Ansamycins are very effective HSP90 inhibitors that showed significant beneficial effects in the treatment of EAE. However, their toxicity and poor stability in solution limit their clinical use. In the present study we have characterized the anti-inflammatory properties of a novel HSP90 inhibitor, PU-H71, and tested its effects in EAE. Our findings show that PU-H71 reduced lipopolysaccharide astrocyte activation but failed to reduce the inflammatory cytokine activation. In contrast to ansamycins, PU-H71 weakly affects EAE clinical course. In conclusion, although PU-H71 displayed some anti-inflammatory properties, it appeared in vivo less effective than the more toxic HSP90 inhibitors. (C) 2012 Elsevier B.V. All rights reserved.