2BYH

3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as Inhibitors of the Hsp90 Molecular Chaperone

Summary for 2BYH

• Entry DOI: 10.2210/pdb2byh/pdb
• Related: 1BYQ 1OSF 1UY6 1UY7 1UY8 1UY9 1UYC 1UYD 1UYE 1UYF 1UYG 1UYH 1UYI 1UYK 1UYL 1YC1 1YC3 1YC4 1YER 1YES 1YET 2BSM 2BT0 2BYI
• Descriptor: HEAT SHOCK PROTEIN HSP90-ALPHA, N-(4-ACETYLPHENYL)-5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDE (3 entities in total)
• Functional Keywords: pyrazole, hsp90, chaperone, atp-binding, heat shock, nucleotide-binding, phosphorylation
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P07900
• Total number of polymer chains: 1
• Total formula weight: 26842.35

Authors

Brough, P.A.,Barril, X.,Beswick, M.,Dymock, B.W.,Drysdale, M.J.,Wright, L.,Grant, K.,Massey, A.,Surgenor, A.,Workman, P. (deposition date: 2005-08-02, release date: 2005-10-12, Last modification date: 2023-12-13)

Primary citation

Brough, P.A.,Barril, X.,Beswick, M.,Dymock, B.W.,Drysdale, M.J.,Wright, L.,Grant, K.,Massey, A.,Surgenor, A.,Workman, P.
3-(5-Chloro-2,4-Dihydroxyphenyl)-Pyrazole-4-Carboxamides as Inhibitors of the Hsp90 Molecular Chaperone.
Bioorg.Med.Chem.Lett., 15:5197-, 2005

PubMed Abstract: Information from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction.

PubMed: 16213716
DOI: 10.1016/J.BMCL.2005.08.091

Experimental method

X-RAY DIFFRACTION (1.9 Å)