Abstract
cAMP-response element binding protein (CREB) is an oncogenic transcription factor implicated in many different types of cancer. We previously reported the discovery of 666-15 as a potent inhibitor of CREB-mediated gene transcription. In an effort to improve the aqueous solubility of 666-15, amino ester prodrugs 1 and 4 were designed and synthesized. Detailed chemical and biological studies of 1 and 4 revealed that a small portion of the prodrugs were converted into 666-15 through intermediate 3 instead of a long-range O,N-acyl transfer reaction that was initially proposed. These results provide unique insights into the activation of these ester prodrugs.
Original language | English (US) |
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Article number | 127455 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 30 |
Issue number | 19 |
DOIs | |
State | Published - Oct 1 2020 |
Keywords
- CREB
- Cancer
- Inhibitor
- Prodrug
- Transcription
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry