Title of article :
The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors
Author/Authors :
Kwai-Ming J. Cheung، نويسنده , , Thomas P. Matthews، نويسنده , , Karen James، نويسنده , , Martin G. Rowlands، نويسنده , , Katherine J. Boxall، نويسنده , , Swee Y. Sharp، نويسنده , , Alison Maloney، نويسنده , , S. Mark Roe، نويسنده , , Chrisostomos Prodromou، نويسنده , , Laurence H. Pearl، نويسنده , , G. Wynne Aherne، نويسنده , , B. Edward McDonald and William L. Siegmann، نويسنده , , Paul Workman، نويسنده ,
Abstract :
High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 μM) inhibitor of Hsp90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical properties. Some initial structure–activity relationships are discussed, as well as the crystal structure of CCT018159 bound to Hsp90.
Keywords :
Hsp90 inhibitors , cancer , Protein crystal structure , resorcinol , Pyrazole
