The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Design, Synthesis, and Biological Evaluation of Hydroquinone Derivatives of 17-Amino-17-demethoxygeldanamycin as Potent, Water-Soluble Inhibitors of Hsp90
Open accessAbstract
17-Allylamino-17-demethoxygeldanamycin (17-AAG)1 is a semisynthetic inhibitor of the 90 kDa heat shock protein (Hsp90) currently in clinical trials for the treatment of cancer. However, 17-AAG faces challenging formulation issues due to its poor solubility. Here we report the synthesis and evaluation of a highly soluble hydroquinone hydrochloride derivative of 17-AAG, 1a (IPI-504), and several of the physiological metabolites. These compounds show comparable binding affinity to human Hsp90 and its endoplasmic reticulum (ER) homologue, the 94 kDa glucose regulated protein (Grp94). Furthermore, the compounds inhibit the growth of the human cancer cell lines SKBR3 and SKOV3, which overexpress Hsp90 client protein Her2, and cause down-regulation of Her2 as well as induction of Hsp70 consistent with Hsp90 inhibition. There is a clear correlation between the measured binding affinity of the compounds and their cellular activities. Upon the basis of its potent activity against Hsp90 and a significant improvement in solubility, 1a is currently under evaluation in Phase I clinical trials for cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Whitesell, L., Mimnaugh, E. G., De Costa, B., Myers, C. E., & Neckers, L. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8324 · Cited by 1,444
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
Epidermal growth factor receptor mutations in lung cancer
Sharma, S. V., Bell, D. W., Settleman, J., & Haber, D. A. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2088 · Cited by 3,170
Natural products to drugs: natural product-derived compounds in clinical trials
Butler, M. S. (2008) · Natural Product Reports · doi:10.1039/b514294f · Cited by 1,075
Drug discovery approaches targeting the PI3K/Akt pathway in cancer
Garcia-Echeverria, C., & Sellers, W. R. (2008) · Oncogene · doi:10.1038/onc.2008.246 · Cited by 473
Brough, P. A., Aherne, W., Barril, X., Borgognoni, J., Boxall, K., Cansfield, J. E., Cheung, K.-M. J., Collins, I., Davies, N. G. M., Drysdale, M. J., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm701018h · Cited by 444
Structures of GRP94-Nucleotide Complexes Reveal Mechanistic Differences between the hsp90 Chaperones
Dollins, D. E., Warren, J. J., Immormino, R. M., & Gewirth, D. T. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.08.024 · Cited by 281
Metadata
- Authors
- Ge, J., Normant, E., Porter, J. R., Ali, J. A., Dembski, M. S., Gao, Y., Georges, A. T., Grenier, L., Pak, R. H., Patterson, J., Sydor, J. R., Tibbitts, T. T., Tong, J. K., Adams, J., & Palombella, V. J.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-06-29
- Volume
- 49
- Issue
- 15
- Pages
- 4606-4615
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2017434303
- Cited by
- 191
- References
- 2
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
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.
