3BM9

Discovery of Benzisoxazoles as Potent Inhibitors of Chaperone Hsp90

Summary for 3BM9

• Entry DOI: 10.2210/pdb3bm9/pdb
• Related: 3BMY
• Descriptor: Heat shock protein HSP 90-alpha, 4-bromo-6-(6-hydroxy-1,2-benzisoxazol-3-yl)benzene-1,3-diol (3 entities in total)
• Functional Keywords: chaperone, atp binding domain, alternative splicing, atp-binding, cytoplasm, nucleotide-binding, phosphoprotein, stress response
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: P07900
• Total number of polymer chains: 1
• Total formula weight: 25734.68

Authors

Gopalsamy, A.,Shi, M.,Vogan, E.M.,Golas, J.,Jacob, J.,Johnson, J.,Lee, F.,Nilakantan, R.,Peterson, R.,Svenson, K.,Tam, M.S.,Wen, Y.,Chopra, R.,Ellingboe, J.,Arndt, K.,Boschelli, F. (deposition date: 2007-12-12, release date: 2008-07-08, Last modification date: 2024-02-21)

Primary citation

Gopalsamy, A.,Shi, M.,Golas, J.,Vogan, E.,Jacob, J.,Johnson, M.,Lee, F.,Nilakantan, R.,Petersen, R.,Svenson, K.,Chopra, R.,Tam, M.S.,Wen, Y.,Ellingboe, J.,Arndt, K.,Boschelli, F.
Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90.
J.Med.Chem., 51:373-375, 2008

PubMed Abstract: Heat shock protein 90 (Hsp90) is a molecular chaperone that is responsible for activating many signaling proteins and is a promising target in tumor biology. We have identified small-molecule benzisoxazole derivatives as Hsp90 inhibitors. Crystallographic studies show that these compounds bind in the ATP binding pocket interacting with the Asp93. Structure based optimization led to the identification of potent analogues, such as 13, with good biochemical profiles.

PubMed: 18197612
DOI: 10.1021/jm701385c

Experimental method

X-RAY DIFFRACTION (1.6 Å)