3EKR

Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone

Summary for 3EKR

• Entry DOI: 10.2210/pdb3ekr/pdb
• Related: 3EKO
• Descriptor: Heat shock protein HSP 90-alpha, 4-{[(2R)-2-(2-methylphenyl)pyrrolidin-1-yl]carbonyl}benzene-1,3-diol, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: hsp90 inhibitors, alternative splicing, atp-binding, chaperone, cytoplasm, nucleotide-binding, phosphoprotein, stress response
• Biological source: Homo sapiens
• Cellular location: Cytoplasm: P07900
• Total number of polymer chains: 2
• Total formula weight: 51855.37

Authors

Gajiwala, K.S. (deposition date: 2008-09-19, release date: 2008-11-25, Last modification date: 2023-08-30)

Primary citation

Kung, P.P.,Funk, L.,Meng, J.,Collins, M.,Zhou, J.Z.,Johnson, M.C.,Ekker, A.,Wang, J.,Mehta, P.,Yin, M.J.,Rodgers, C.,Davies, J.F.,Bayman, E.,Smeal, T.,Maegley, K.A.,Gehring, M.R.
Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone.
Bioorg.Med.Chem.Lett., 18:6273-6278, 2008

PubMed Abstract: Information from X-ray crystal structures were used to optimize the potency of a HTS hit in a Hsp90 competitive binding assay. A class of novel and potent small molecule Hsp90 inhibitors were thereby identified. Enantio-pure compounds 31 and 33 were potent in PGA-based competitive binding assay and inhibited proliferation of various human cancer cell lines in vitro, with IC(50) values averaging 20 nM.

PubMed: 18929486
DOI: 10.1016/j.bmcl.2008.09.081

Experimental method

X-RAY DIFFRACTION (2 Å)