An Hsp90 modulator that exhibits a unique mechanistic profile.
Bioorg Med Chem Lett
; 22(9): 3287-90, 2012 May 01.
Article
en En
| MEDLINE
| ID: mdl-22480433
ABSTRACT
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 derivatives, we show that the macrocycle does not inhibit binding between C-terminal client proteins and co-chaperones and Hsp90, suggesting that it has a unique mechanism of action.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas HSP90 de Choque Térmico
/
Compuestos Macrocíclicos
Límite:
Animals
/
Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article