PDBsum entry 3bet

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Lyase PDB id
Protein chain
258 a.a.
Waters ×292

References listed in PDB file
Key reference
Title Structure-Activity relationships of c-17 cyano-Substituted estratrienes as anticancer agents.
Authors M.P.Leese, F.L.Jourdan, K.Gaukroger, M.F.Mahon, S.P.Newman, P.A.Foster, C.Stengel, S.Regis-Lydi, E.Ferrandis, A.Di fiore, G.De simone, C.T.Supuran, A.Purohit, M.J.Reed, B.V.Potter.
Ref. J Med Chem, 2008, 51, 1295-1308. [DOI no: 10.1021/jm701319c]
PubMed id 18260615
The synthesis, SAR, and preclinical evaluation of 17-cyanated 2-substituted estra-1,3,5(10)-trienes as anticancer agents are discussed. 2-Methoxy-17beta-cyanomethylestra-1,3,5(10)-trien-3-ol ( 14), but not the related 2-ethyl derivative 7, and the related 3- O-sulfamates 8 and 15 display potent antiproliferative effects (MCF-7 GI 50 300, 60 and 70 nM, respectively) against human cancer cells in vitro. Investigation of the SAR reveals that a sterically unhindered hydrogen bond acceptor attached to C-17 is most likely key to the enhanced activity. Compound 8 displayed significant in vitro antiangiogenic activity, and its ability to act as a microtubule disruptor was confirmed. Inhibitory activity of the sulfamate derivatives against steroid sulfatase and carbonic anhydrase II (hCAII) was also observed, and the interaction between 15 and hCAII was investigated by protein crystallography. The potential of these multimechanism anticancer agents was confirmed in vivo, with promising activity observed for both 14 and 15 in an athymic nude mouse MDA-MB-231 human breast cancer xenograft model.
Secondary reference #1
Title Refined structure of human carbonic anhydrase ii at 2.0 a resolution.
Authors A.E.Eriksson, T.A.Jones, A.Liljas.
Ref. Proteins, 1988, 4, 274-282.
PubMed id 3151019
Secondary reference #2
Title 2-Substituted estradiol bis-Sulfamates, Multitargeted antitumor agents: synthesis, In vitro sar, Protein crystallography, And in vivo activity.
Authors M.P.Leese, B.Leblond, A.Smith, S.P.Newman, A.Di fiore, G.De simone, C.T.Supuran, A.Purohit, M.J.Reed, B.V.Potter.
Ref. J Med Chem, 2006, 49, 7683-7696. [DOI no: 10.1021/jm060705x]
PubMed id 17181151
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