ArticleACS medicinal chemistry letters2014
Novel Type of Prodrug Activation through a Long-Range O,N-Acyl Transfer: A Case of Water-Soluble CREB Inhibitor.
Article in ACS medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- SARS-CoV-2 infection activates CREB/CBP in cellular cyclic AMP-dependent pathways.Journal of medical virology · 2023Article
- Review
- A Photodeactivatable Antagonist for Controlling CREB-Dependent Gene Expression.ACS central science · 2020Article
- What turns CREB on? And off? And why does it matter?Cellular and molecular life sciences : CMLS · 2020Review
- Mechanistic insights into the activation of ester prodrugs of 666-15.Bioorganic & medicinal chemistry letters · 2020Article
- Direct Targeting of CREB1 with Imperatorin Inhibits TGFAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- A suite of bioassays to evaluate CREB inhibitors.Methods in enzymology · 2020Article
- Discovery of a Synergistic Inhibitor of cAMP-Response Element Binding Protein (CREB)-Mediated Gene Transcription withJournal of medicinal chemistry · 2019Article
- Design, synthesis and evaluation of antitumor acylated monoaminopyrroloquinazolines.Bioorganic & medicinal chemistry letters · 2017Article
- Design, synthesis and biological evaluation of regioisomers of 666-15 as inhibitors of CREB-mediated gene transcription.Bioorganic & medicinal chemistry letters · 2017Article
- Systemic Inhibition of CREB is Well-tolerated in vivo.Scientific reports · 2016Article
- Identification of a Potent Inhibitor of CREB-Mediated Gene Transcription with Efficacious in Vivo Anticancer Activity.Journal of medicinal chemistry · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CREB (cAMP response element binding protein) has been shown to play an important role in tumor initiation, progression, and metastasis. We discovered that naphthol AS-E, a cell-permeable CREB inhibitor, presented antiproliferative activity in a broad panel of cancer cell lines in vitro. However, it has limited aqueous solubility. In this report, we described a water-soluble inhibitor (compound 6) of CREB-mediated gene transcription with in vivo anticancer activity. Unexpectedly, compound 6 was found to be a prodrug of compound 12 necessitating an unprecedented long-range O,N-acyl transfer. The rate of this transfer was pH- and temperature-dependent. To the best of our knowledge, this is the first time to show that a long-range O,N-acyl transfer could be exploited as a prodrug activation strategy to improve aqueous solubility. This type of prodrug may be applicable to other structures with spatially arranged hydroxyl amide to improve their aqueous solubility.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.