Novel Aminophenyl Benzamide-Type Histone Deacetylase Inhibitors with Enhanced Potency and Selectivity
Abstract
Significant effort is being made to understand the role of HDAC isotypes in human cancer and to develop antitumor agents with better therapeutic windows. A part of this endeavor was the exploration of the 14 A internal cavity adjacent to the enzyme catalytic site, which led to the design and synthesis of compound 4 with the unusual bis(aryl)-type pharmacophore. SAR studies around this lead resulted in optimization to potent, selective, nonhydroxamic acid HDAC inhibitors.
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CI-994 is an analog of niclosamide.
“Interesting, a recent study has shown that CI-994 (Fig. 1A), an analog of niclosamide and an inhibitor of class I HDACs [39], is able to enhance the TCF/LEF reporter activity of Wnt/β-catenin signaling [40], suggesting that CI-994 could display an opposite effect on Wnt/β-catenin signaling.”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [39]
CI-994 is an inhibitor of class I HDACs.
“Interesting, a recent study has shown that CI-994 (Fig. 1A), an analog of niclosamide and an inhibitor of class I HDACs [39], is able to enhance the TCF/LEF reporter activity of Wnt/β-catenin signaling [40], suggesting that CI-994 could display an opposite effect on Wnt/β-catenin signaling.”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [39]
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- Authors
- Moradei, O. M., Mallais, T. C., Frechette, S., Paquin, I., Tessier, P. E., Leit, S. M., Fournel, M., Bonfils, C., Trachy-Bourget, M.-C., Liu, J., Yan, T. P., Lu, A.-H., Rahil, J., Wang, J., Lefebvre, S., Li, Z., Vaisburg, A. F., & Besterman, J. M.
- Affiliations
- MethylGene Inc, 7220 Frederick-Banting, Montréal, QC H4S 2A1, Canada
- ORCID
- Liu, Jianhong
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-10-17
- Volume
- 50
- Issue
- 23
- Pages
- 5543-5546
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2042828682
- Cited by
- 166
- References
- 3
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 9 · 2023: 12 · 2022: 6 · 2021: 8 · 2020: 11 · 2019: 7 · 2018: 10 · 2017: 12 · 2016: 9 · 2015: 6 · 2014: 14 · 2013: 11 · 2012: 4
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Keywords
- histone deacetylase inhibitors, structure-activity relationship, anticancer agents
- MeSH terms
- Antineoplastic Agents, Benzamides, Cell Line, Histone Deacetylases, Humans, Models, Molecular, NADH, NADPH Oxidoreductases, Structure-Activity Relationship, Catalytic Domain, Histone Deacetylase 1, Histone Deacetylase Inhibitors
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