PDBsum entry 2zdu

Transferase

PDB id: 2zdu

Contents

Protein chain

330 a.a.

Ligands

446

Waters ×58

References listed in PDB file

Key reference

• Title: Discovery, Synthesis and biological evaluation of isoquinolones as novel and highly selective jnk inhibitors (1).
• Authors: Y.Asano, S.Kitamura, T.Ohra, K.Aso, H.Igata, T.Tamura, T.Kawamoto, T.Tanaka, S.Sogabe, S.Matsumoto, M.Yamaguchi, H.Kimura, F.Itoh.
• Ref.: Bioorg Med Chem Lett, 2008, 16, 4715-4732. [DOI no: 10.1016/j.bmc.2008.02.027]
• PubMed id: 18313304

Abstract

A novel series of 4-phenylisoquinolones were synthesized and evaluated as c-Jun N-terminal kinase (JNK) inhibitors. Initial modification at the 2- and 3-positions of the isoquinolone ring of hit compound 4, identified from high-throughput screening, led to the lead compound 6b. The optimization was carried out using a JNK1-binding model of 6b and several compounds exhibited potent JNK inhibition. Among them, 11g significantly inhibited cardiac hypertrophy in rat pressure-overload models without affecting blood pressure and the concept of JNK inhibitors as novel therapeutic agents for heart failure was confirmed.