The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a Novel Inhibitor of the Molecular Chaperone Hsp90 by Fragment Based Drug Design
Abstract
Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) are currently generating significant interest in clinical development as potential treatments for cancer. In a preceding publication (DOI: 10.1021/jm100059d ) we describe Astex's approach to screening fragments against Hsp90 and the subsequent optimization of two hits into leads with inhibitory activities in the low nanomolar range. This paper describes the structure guided optimization of the 2,4-dihydroxybenzamide lead molecule 1 and details some of the drug discovery strategies employed in the identification of AT13387 (35), which has progressed through preclinical development and is currently being tested in man.
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Cites
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Cited by
Induced protein degradation: an emerging drug discovery paradigm
Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486
The role of ligand efficiency metrics in drug discovery
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Self-citationHsp90 Molecular Chaperone Inhibitors: Are We There Yet?
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Fragment-Based Approaches in Drug Discovery and Chemical Biology
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Targeting protein–protein interactions as an anticancer strategy
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Metadata
- Authors
- Woodhead, A. J., Angove, H., Carr, M. G., Chessari, G., Congreve, M., Coyle, J. E., Cosme, J., Graham, B., Day, P. J., Downham, R., Fazal, L., Feltell, R., Figueroa, E., Frederickson, M., Lewis, J., McMenamin, R., Murray, C. W., O’Brien, M. A., Parra, L., Patel, S., Phillips, T., Rees, D. C., Rich, S., Smith, D.-M., Trewartha, G., Vinkovic, M., Williams, B., & Woolford, A. J.-A.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-07-28
- Volume
- 53
- Issue
- 16
- Pages
- 5956-5969
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2141715793
- Cited by
- 264
- References
- 58
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a Novel Inhibitor of the Molecular Chaperone Hsp90 by Fragment Based Drug Design. https://app.cochat.ai/papers/10.1021/jm100060b
- The paper
- Woodhead, A. J., Angove, H., Carr, M. G., Chessari, G., Congreve, M., Coyle, J. E., Cosme, J., Graham, B., Day, P. J., Downham, R., Fazal, L., Feltell, R., Figueroa, E., Frederickson, M., Lewis, J., McMenamin, R., Murray, C. W., O’Brien, M. A., Parra, L., . . . Woolford, A. J.-A. (2010). Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a Novel Inhibitor of the Molecular Chaperone Hsp90 by Fragment Based Drug Design. Journal of Medicinal Chemistry. https://doi.org/10.1021/jm100060b
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
