2BT0

Novel, potent small molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design

Summary for 2BT0

• Entry DOI: 10.2210/pdb2bt0/pdb
• Related: 1BYQ 1OSF 1UY6 1UY7 1UY8 1UY9 1UYC 1UYD 1UYE 1UYF 1UYG 1UYH 1UYI 1UYK 1UYL 1YC1 1YC3 1YC4 1YER 1YES 1YET 2BSM
• Descriptor: HEAT SHOCK PROTEIN HSP90-ALPHA, 4-[4-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)-3-METHYL-1H-PYRAZOL-5-YL]-6-ETHYLBENZENE-1,3-DIOL (3 entities in total)
• Functional Keywords: atp-binding, chaperone, heat shock, phosphorylation
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus : P07900
• Total number of polymer chains: 2
• Total formula weight: 53645.92

Authors

Dymock, B.W.,Barril, X.,Brough, P.A.,Cansfield, J.E.,Massey, A.,McDonald, E.,Hubbard, R.E.,Surgenor, A.,Roughley, S.D.,Webb, P.,Workman, P.,Wright, L.,Drysdale, M.J. (deposition date: 2005-05-24, release date: 2005-06-02, Last modification date: 2023-12-13)

Primary citation

Dymock, B.W.,Barril, X.,Brough, P.A.,Cansfield, J.E.,Massey, A.,McDonald, E.,Hubbard, R.E.,Surgenor, A.,Roughley, S.D.,Webb, P.,Workman, P.,Wright, L.,Drysdale, M.J.
Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design.
J. Med. Chem., 48:4212-4215, 2005

PubMed Abstract: The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmacodynamic changes. Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG.

PubMed: 15974572
DOI: 10.1021/jm050355z

Experimental method

X-RAY DIFFRACTION (1.9 Å)