Design and synthesis of a new, conformationally constrained, macrocyclic small-molecule inhibitor of STAT3 via 'click chemistry'.
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.
Chen
Jianyong
J
University of Michigan Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Nikolovska-Coleska
Zaneta
Z
Yang
Chao-Yie
CY
Gomez
Cindy
C
Gao
Wei
W
Krajewski
Krzysztof
K
Jiang
Sheng
S
Roller
Peter
P
Wang
Shaomeng
S
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D005454:Fluorescence Polarization; D008958:Models, Molecular; D008968:Molecular Conformation; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor