PDBsum entry 1yrs

Cell cycle

PDB id: 1yrs

Contents

Protein chains

330 a.a.

Ligands

ADP ×2

L47 ×2

Metals

_MG ×2

Waters ×166

References listed in PDB file

Key reference

• Title: Kinesin spindle protein (ksp) inhibitors. Part 1: the discovery of 3,5-Diaryl-4,5-Dihydropyrazoles as potent and selective inhibitors of the mitotic kinesin ksp.
• Authors: C.D.Cox, M.J.Breslin, B.J.Mariano, P.J.Coleman, C.A.Buser, E.S.Walsh, K.Hamilton, H.E.Huber, N.E.Kohl, M.Torrent, Y.Yan, L.C.Kuo, G.D.Hartman.
• Ref.: Bioorg Med Chem Lett, 2005, 15, 2041-2045. [DOI no: 10.1016/j.bmcl.2005.02.055]
• PubMed id: 15808464

Abstract

Optimization of high-throughput screening (HTS) hits resulted in the discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of KSP. Dihydropyrazole 15 is a potent, cell-active KSP inhibitor that induces apoptosis and generates aberrant mitotic spindles in human ovarian carcinoma cells at low nanomolar concentrations. X-ray crystallographic evidence is presented which demonstrates that these inhibitors bind in an allosteric pocket of KSP distant from the nucleotide and microtubule binding sites.