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PDBsum entry 2ccs
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References listed in PDB file
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Key reference
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Title
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4-Amino derivatives of the hsp90 inhibitor cct018159.
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Authors
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X.Barril,
M.C.Beswick,
A.Collier,
M.J.Drysdale,
B.W.Dymock,
A.Fink,
K.Grant,
R.Howes,
A.M.Jordan,
A.Massey,
A.Surgenor,
J.Wayne,
P.Workman,
L.Wright.
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Ref.
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Bioorg Med Chem Lett, 2006,
16,
2543-2548.
[DOI no: ]
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PubMed id
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Abstract
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Novel piperazinyl, morpholino and piperidyl derivatives of the pyrazole-based
Hsp90 inhibitor CCT018159 are described. Structure-activity relationships have
been elucidated by X-ray co-crystal analysis of the new compounds bound to the
N-terminal domain of human Hsp90. Key features of the binding mode are
essentially identical to the recently reported potent analogue VER-49009. The
most potent of the new compounds has a methylsulfonylbenzyl substituent appended
to the piperazine nitrogen, possesses an IC50 of less than 600 nM binding
against the enzyme and demonstrates low micromolar inhibition of tumour cell
proliferation.
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