The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin.

摘要: Purpose: Benzoquinone ansamycins are antibiotics with anticancer potential. First described as tyrosine kinase inhibitors, they now frequently used to target HSP90 chaperone function. While herbimycin A and geldanamycin (GA) have been widely in preclinical studies, both drugs poor candidates for clinical trials owing their vivo toxicity lack of stability. We therefore examined the biologic effects 17-allylamino-17-demethoxygeldanamycin (17-AG), an ansamycin derivative lower than GA. Methods: Binding 17-AG was studied vitro using a GA-affinity beads competition assay. analyzed drug-induced destabilization p185erbB2, Raf-1 mutant p53 SKBR3 breast cancer cells by Western blotting. The antiproliferative activities GA were compared MTT Results: found that, similar manner itself, bound specifically HSP90. It also led degradation receptor serine/threonine p53. Both displayed comparable MCF7 cells. Even though binding weaker GA, caused tumor at doses. Conclusion: shares important features its parent compound Since has better profile it is interesting candidate benzoquinone development.