PDBsum entry 2fme

Cell cycle

PDB id: 2fme

Contents

Protein chains

321 a.a.

Ligands

3QC ×2

ADP ×2

Metals

_MG ×2

Waters ×178

References listed in PDB file

Key reference

• Title: Inhibitors of human mitotic kinesin eg5: characterization of the 4-Phenyl-Tetrahydroisoquinoline lead series.
• Authors: C.M.Tarby, R.F.Kaltenbach, T.Huynh, A.Pudzianowski, H.Shen, M.Ortega-Nanos, S.Sheriff, J.A.Newitt, P.A.Mcdonnell, N.Burford, C.R.Fairchild, W.Vaccaro, Z.Chen, R.M.Borzilleri, J.Naglich, L.J.Lombardo, M.Gottardis, G.L.Trainor, D.L.Roussell.
• Ref.: Bioorg Med Chem Lett, 2006, 16, 2095-2100. [DOI no: 10.1016/j.bmcl.2006.01.056]
• PubMed id: 16458511

Abstract

In a high-throughput screening effort, a series of tetrahydroisoquinolines was identified as modest inhibitors of human Eg5. A medicinal chemistry optimization effort led to the identification of R-4-(3-hydroxyphenyl)-N,N-7,8-tetramethyl-3,4-dihydroisoquinoline-2(1H)-carboxamide (32a) as a potent inhibitor of human Eg5 (ATPase IC50 104 nM) with good anti-proliferative activity in A2780 cells (IC50 234 nM).