Design and synthesis of a new, conformationally constrained, macrocyclic small-molecule inhibitor of STAT3 via 'click chemistry'

Jianyong Chen; Zaneta Nikolovska-Coleska; Chao-Yie Yang; Cindy Gomez; Wei Gao; Krzysztof Krajewski; Sheng Jiang; Peter Roller; Shaomeng Wang

doi:10.1016/j.bmcl.2007.04.096

Design and synthesis of a new, conformationally constrained, macrocyclic small-molecule inhibitor of STAT3 via 'click chemistry'

Bioorg Med Chem Lett. 2007 Jul 15;17(14):3939-42. doi: 10.1016/j.bmcl.2007.04.096. Epub 2007 May 3.

Authors

Jianyong Chen¹, Zaneta Nikolovska-Coleska, Chao-Yie Yang, Cindy Gomez, Wei Gao, Krzysztof Krajewski, Sheng Jiang, Peter Roller, Shaomeng Wang

Affiliation

¹ University of Michigan Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

PMID: 17513110
DOI: 10.1016/j.bmcl.2007.04.096

Abstract

STAT3 is a promising molecular target for the design of new anticancer drugs. In this paper, we report the design and synthesis of a conformationally constrained macrocyclic peptidomimetic 2 via click chemistry. Compound 2 was determined to bind to STAT3 with a K(i) value of 7.3 microM in a competitive fluorescence-polarization-based binding assay, representing a promising initial lead compound for further optimization.

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Drug Design
Fluorescence Polarization
Models, Molecular
Molecular Conformation
STAT3 Transcription Factor / antagonists & inhibitors*

Substances

Antineoplastic Agents
STAT3 Transcription Factor