PDBsum entry 2gd8

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Lyase PDB id
Protein chain
257 a.a.
PO1 ×2
Waters ×321

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Key reference
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
The anticancer activities and SARs of estradiol-17-O-sulfamates and estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) as steroid sulfatase (STS) inhibitors and antiproliferative agents are discussed. Estradiol 3,17-O,O-bis-sulfamates 20 and 21, in contrast to the 17-O-monosulfamate 11, proved to be excellent STS inhibitors. 2-Substituted E2bisMATEs 21 and 23 additionally exhibited potent antiproliferative activity with mean graph midpoint values of 18-87 nM in the NCI 60-cell-line panel. 21 Exhibited antiangiogenic in vitro and in vivo activity in an early-stage Lewis lung model, and 23 dosed p.o. caused marked growth inhibition in a nude mouse xenograft tumor model. Modeling studies suggest that the E2bisMATEs and 2-MeOE2 share a common mode of binding to tubulin, though COMPARE analysis of activity profiles was negative. 21 was cocrystallized with carbonic anhydrase II, and X-ray crystallography revealed unexpected coordination of the 17-O-sulfamate of 21 to the active site zinc and a probable additional lower affinity binding site. 2-Substituted E2bisMATEs are attractive candidates for further development as multitargeted anticancer agents.
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