Synthesis of Hsp90 inhibitor dimers as potential antitumor agents.
Bioorg Med Chem
; 16(11): 5862-70, 2008 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-18487051
ABSTRACT
Structure-based drug design was used to systematically synthesize PU3-dimers. The cytotoxicity of PU3 dimers 6 against breast cancer cell lines was evaluated, and their potency increased as the length of the bridging linker increased. Among the compounds tested, 6e with a C-20 linker was the most potent and exhibited a 20- to 30-fold increase in activity compared with that of the parent compound 5. Western blot analyses of the cell lysates treated with 6c revealed that 6c resulted in the concentration-dependent degradation of the Hsp90 client protein Her2, which is consistent with other Hsp90 inhibitors.
Full text:
1
Database:
MEDLINE
Main subject:
Adenine
/
HSP90 Heat-Shock Proteins
/
Anisoles
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Year:
2008
Type:
Article