PDBsum entry 2j4z

Transferase

PDB id: 2j4z

Contents

Protein chains

264 a.a.

Ligands

626 ×2

ARS ×3

Waters ×194

References listed in PDB file

Key reference

• Title: 1,4,5,6-Tetrahydropyrrolo[3,4-C]pyrazoles: identification of a potent aurora kinase inhibitor with a favorable antitumor kinase inhibition profile.
• Authors: D.Fancelli, J.Moll, M.Varasi, R.Bravo, R.Artico, D.Berta, S.Bindi, A.Cameron, I.Candiani, P.Cappella, P.Carpinelli, W.Croci, B.Forte, M.L.Giorgini, J.Klapwijk, A.Marsiglio, E.Pesenti, M.Rocchetti, F.Roletto, D.Severino, C.Soncini, P.Storici, R.Tonani, P.Zugnoni, P.Vianello.
• Ref.: J Med Chem, 2006, 49, 7247-7251. [DOI no: 10.1021/jm060897w]
• PubMed id: 17125279

Abstract

The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.