An Hsp90 modulator that exhibits a unique mechanistic profile.
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ABSTRACT:
SUBMITTER: Ramsey DM
PROVIDER: S-EPMC3337333 | biostudies-literature | 2012 May
REPOSITORIES: biostudies-literature
Publications
An Hsp90 modulator that exhibits a unique mechanistic profile.
Ramsey Deborah M DM McConnell Jeanette R JR Alexander Leslie D LD Tanaka Kaishin W KW Vera Chester M CM McAlpine Shelli R SR
Bioorganic & medicinal chemistry letters 20120311 9
Described is the synthesis of two biotinylated derivatives of a cytotoxic macrocycle. Pull-down assays indicate that this macrocycle targets the N-middle domain of Hsp90. Untagged compound can effectively compete away tagged compound-Hsp90 protein complexes, confirming the binding specificity of the macrocycle for Hsp90. The macrocycle is similar in potency to other structurally-related analogs of Sansalvamide A (San A) and induces apoptosis via a caspase 3 mechanism. Unlike other San A derivati ...[more]
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