PDBsum entry 2fl2

Cell cycle

PDB id: 2fl2

Contents

Protein chains

330 a.a.

Ligands

ADP ×2

N4T ×2

Metals

_MG ×2

Waters ×129

References listed in PDB file

Key reference

• Title: Kinesin spindle protein (ksp) inhibitors. Part 2: the design, Synthesis, And characterization of 2,4-Diaryl-2,5-Dihydropyrrole inhibitors of the mitotic kinesin ksp.
• Authors: M.E.Fraley, R.M.Garbaccio, K.L.Arrington, W.F.Hoffman, E.S.Tasber, P.J.Coleman, C.A.Buser, E.S.Walsh, K.Hamilton, C.Fernandes, M.D.Schaber, R.B.Lobell, W.Tao, V.J.South, Y.Yan, L.C.Kuo, T.Prueksaritanont, C.Shu, M.Torrent, D.C.Heimbrook, N.E.Kohl, H.E.Huber, G.D.Hartman.
• Ref.: Bioorg Med Chem Lett, 2006, 16, 1775-1779. [DOI no: 10.1016/j.bmcl.2006.01.030]
• PubMed id: 16439123

Abstract

The evolution of 2,4-diaryl-2,5-dihydropyrroles as inhibitors of KSP is described. Introduction of basic amide and urea moieties to the dihydropyrrole nucleus enhanced potency and aqueous solubility, simultaneously, and provided compounds that caused mitotic arrest of A2780 human ovarian carcinoma cells with EC(50)s<10nM. Ancillary hERG activity was evaluated for this series of inhibitors.