The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Fragment-Based Drug Discovery Applied to Hsp90. Discovery of Two Lead Series with High Ligand Efficiency
Open accessAbstract
Inhibitors of the chaperone Hsp90 are potentially useful as chemotherapeutic agents in cancer. This paper describes an application of fragment screening to Hsp90 using a combination of NMR and high throughput X-ray crystallography. The screening identified an aminopyrimidine with affinity in the high micromolar range and subsequent structure-based design allowed its optimization into a low nanomolar series with good ligand efficiency. A phenolic chemotype was also identified in fragment screening and was found to bind with affinity close to 1 mM. This fragment was optimized using structure based design into a resorcinol lead which has subnanomolar affinity for Hsp90, excellent cell potency, and good ligand efficiency. This fragment to lead campaign improved affinity for Hsp90 by over 1,000,000-fold with the addition of only six heavy atoms. The companion paper (DOI: 10.1021/jm100060b) describes how the resorcinol lead was optimized into a compound that is now in clinical trials for the treatment of cancer.
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Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139
HSP90 and the chaperoning of cancer
Whitesell, L., & Lindquist, S. L. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1716 · Cited by 2,502
The influence of drug-like concepts on decision-making in medicinal chemistry
Leeson, P. D., & Springthorpe, B. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2445 · Cited by 2,403
Roe, S. M., Prodromou, C., O'Brien, R., Ladbury, J. E., Piper, P. W., & Pearl, L. H. (1999) · Journal of Medicinal Chemistry · doi:10.1021/jm980403y · Cited by 1,004
Cited by
The role of ligand efficiency metrics in drug discovery
Hopkins, A. L., Keserü, G. M., Leeson, P. D., Rees, D. C., & Reynolds, C. H. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4163 · Cited by 1,181
Fragment-Based Approaches in Drug Discovery and Chemical Biology
Scott, D. E., Coyne, A. G., Hudson, S. A., & Abell, C. (2012) · Biochemistry · doi:10.1021/bi3005126 · Cited by 460
Targeting protein–protein interactions as an anticancer strategy
Ivanov, A. A., Khuri, F. R., & Fu, H. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.04.007 · Cited by 401
Woodhead, A. J., Angove, H., Carr, M. G., Chessari, G., Congreve, M., Coyle, J. E., Cosme, J., Graham, B., Day, P. J., Downham, R., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100060b · Cited by 264
Self-citationOld and New Approaches to Target the Hsp90 Chaperone
Sanchez, J., Carter, T. R., Cohen, M. S., & Blagg, B. S. J. (2020) · Current Cancer Drug Targets · doi:10.2174/1568009619666191202101330 · Cited by 183
Metadata
- Authors
- Murray, C. W., Carr, M. G., Callaghan, O., Chessari, G., Congreve, M., Cowan, S., Coyle, J. E., Downham, R., Figueroa, E., Frederickson, M., Graham, B., McMenamin, R., O’Brien, M. A., Patel, S., Phillips, T. R., Williams, G., Woodhead, A. J., & Woolford, A. J.-A.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-07-27
- Volume
- 53
- Issue
- 16
- Pages
- 5942-5955
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2110845358
- Cited by
- 184
- References
- 4
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- green
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- Murray, C. W., Carr, M. G., Callaghan, O., Chessari, G., Congreve, M., Cowan, S., Coyle, J. E., Downham, R., Figueroa, E., Frederickson, M., Graham, B., McMenamin, R., O’Brien, M. A., Patel, S., Phillips, T. R., Williams, G., Woodhead, A. J., & Woolford, A. J.-A. (2010). Fragment-Based Drug Discovery Applied to Hsp90. Discovery of Two Lead Series with High Ligand Efficiency. Journal of Medicinal Chemistry. https://doi.org/10.1021/jm100059d
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
