Design, synthesis, and evaluation of peptidomimetics containing Freidinger lactams as STAT3 inhibitors

Cindy Gomez; Longchuan Bai; Jian Zhang; Zaneta Nikolovska-Coleska; Jianyong Chen; Han Yi; Shaomeng Wang

doi:10.1016/j.bmcl.2009.01.091

Design, synthesis, and evaluation of peptidomimetics containing Freidinger lactams as STAT3 inhibitors

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1733-6. doi: 10.1016/j.bmcl.2009.01.091. Epub 2009 Jan 31.

Authors

Cindy Gomez¹, Longchuan Bai, Jian Zhang, Zaneta Nikolovska-Coleska, Jianyong Chen, Han Yi, Shaomeng Wang

Affiliation

¹ Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.

PMID: 19243938
DOI: 10.1016/j.bmcl.2009.01.091

Abstract

The STAT3 oncogene is a promising molecular target for the design of a new class of anticancer drugs. In this letter, we describe the design, synthesis, and evaluation of peptidomimetics containing Freidinger lactams as novel STAT3 inhibitors. Compound 3 binds to STAT3 with a K(i) value of 190nM and is a promising lead compound for further design and optimization.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Biomimetics
Chemistry, Pharmaceutical / methods*
Drug Design
Drug Screening Assays, Antitumor
Humans
Kinetics
Lactams / chemical synthesis*
Lactams / pharmacology
Models, Chemical
Molecular Structure
Phosphopeptides / chemistry
Phosphorylation
Protein Conformation
STAT3 Transcription Factor / antagonists & inhibitors*
STAT3 Transcription Factor / chemistry*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Lactams
Phosphopeptides
STAT3 Transcription Factor