Work

Discovery of a Synergistic Inhibitor of cAMP-Response Element Binding Protein (CREB)-Mediated Gene Transcription with 666 - 15

Year: 2019

Type: article

Abstract: CREB is a transcription factor implicated in the pathogenesis of multiple cancers. Targeting CREB is a promising strategy to develop potential cancer therapeutics. Previously, we identified 666 - 15 as a potent CREB inhibitor. Herein, we designed an ester prodrug of 666 - 15 through a long-range O, N -acyl transfer reaction for improved aqueous solubility. Unexpectedly, we discovered a small molecule 11 ( 653 - 47 ) that can potentiate the CREB inhibitory activity of 666 - 15 although 653 - 47 alone does not inhibit CREB.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/acs.jmedchem.9b01207

Authors: Fuchun Xie, Qiuhua Fan, Bingbing X. Li, Xiangshu Xiao

Institutions: Oregon Health & Science University, OHSU Knight Cancer Institute

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green