The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma
Open accessAbstract
The t(4;14) translocation that occurs uniquely in a subset (15%) of patients with multiple myeloma (MM) results in the ectopic expression of the receptor tyrosine kinase (RTK), fibroblast growth factor receptor 3 (FGFR3). Inhibition of activated FGFR3 in MM cells induces apoptosis, validating FGFR3 as a therapeutic target in t(4;14) MM and encouraging the clinical development of FGFR3 inhibitors for the treatment of these patients, who have a poor prognosis. We describe here the characterization of a novel, small-molecule inhibitor of class III, IV, and V RTKs, CHIR-258, as an inhibitor of FGFR3. CHIR-258 potently inhibits FGFR3 with an inhibitory concentration of 50% (IC50) of 5 nM in in vitro kinase assays and selectively inhibited the growth of B9 cells and human myeloma cell lines expressing wild-type (WT) or activated mutant FGFR3. In responsive cell lines, CHIR-258 induced cytostatic and cytotoxic effects. Importantly, addition of interleukin 6 (IL-6) or insulin growth factor 1 (IGF-1) or coculture on stroma did not confer resistance to CHIR-258. In primary myeloma cells from t(4;14) patients, CHIR-258 inhibited downstream extracellular signal-regulated kinase (ERK) 1/2 phosphorylation with an associated cytotoxic response. Finally, therapeutic efficacy of CHIR-258 was demonstrated in a xenograft mouse model of FGFR3 MM. These studies support the clinical evaluation of CHIR-258 in MM.
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
Slamon, D. J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eiermann, W., Wolter, J., Pegram, M., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103153441101 · Cited by 11,500
Druker, B. J., Talpaz, M., Resta, D. J., Peng, B., Buchdunger, E., Ford, J. M., Lydon, N. B., Kantarjian, H., Capdeville, R., Ohno-Jones, S., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104053441401 · Cited by 5,243
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors
Demetri, G. D., von Mehren, M., Blanke, C. D., Van den Abbeele, A. D., Eisenberg, B., Roberts, P. J., Heinrich, M. C., Tuveson, D. A., Singer, S., Janicek, M., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020461 · Cited by 4,389
Druker, B. J., Sawyers, C. L., Kantarjian, H., Resta, D. J., Reese, S. F., Ford, J. M., Capdeville, R., & Talpaz, M. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104053441402 · Cited by 2,713
Attal, M., Harousseau, J.-L., Stoppa, A.-M., Sotto, J.-J., Fuzibet, J.-G., Rossi, J.-F., Casassus, P., Maisonneuve, H., Facon, T., Ifrah, N., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199607113350204 · Cited by 2,548
Ttal, M. I. A., Ean, J., Dünne, A. A., Toppa, A. S., Ossi, R. G., Hilippe, P., Asassus, C., Acon, T. H. F., Orbert, N., Ayen, C. A. P., et al. (2013) · Cited by 2,161
Vogel, C. L., Cobleigh, M. A., Tripathy, D., Gutheil, J. C., Harris, L. N., Fehrenbacher, L., Slamon, D. J., Murphy, M., Novotny, W. F., Burchmore, M., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.20.3.719 · Cited by 1,860
KIT activation is a ubiquitous feature of gastrointestinal stromal tumors.
Rubin, B. P., Singer, S., Tsao, C., Duensing, A. U., Lux, M. L., Ruiz, R., Hibbard, M. K., Chen, C. J., Xiao, S., Tuveson, D. A., et al. (2001) · PubMed · Cited by 959
Self-citationMultiple myeloma: evolving genetic events and host interactions
Kuehl, W. M., & Bergsagel, P. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc746 · Cited by 818
Single Cell Profiling of Potentiated Phospho-Protein Networks in Cancer Cells
Irish, J. M., Hovland, R., Krutzik, P. O., Perez, O. D., Bruserud, Ø., Gjertsen, B. T., & Nolan, G. P. (2004) · Cell · doi:10.1016/j.cell.2004.06.028 · Cited by 684
Cited by
A quantitative analysis of kinase inhibitor selectivity
Karaman, M. W., Herrgard, S., Treiber, D. K., Gallant, P., Atteridge, C. E., Campbell, B. T., Chan, K. W., Ciceri, P., Davis, M. I., Edeen, P. T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1358 · Cited by 2,466
Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets
Hideshima, T., Mitsiades, C., Tonon, G., Richardson, P. G., & Anderson, K. C. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2189 · Cited by 932
FGF/FGFR signaling in health and disease
Xie, Y., Su, N., Yang, J., Tan, Q., Huang, S., Jin, M., Ni, Z., Zhang, B., Zhang, D., Luo, F., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00222-7 · Cited by 904
International Myeloma Working Group molecular classification of multiple myeloma: spotlight review
Fonseca, R., Bergsagel, P. L., Drach, J., Shaughnessy, J., Gutierrez, N., Stewart, A. K., Morgan, G., Van Ness, B., Chesi, M., Minvielle, S., et al. (2009) · Leukemia · doi:10.1038/leu.2009.174 · Cited by 886
Self-citationAdvances and challenges in targeting FGFR signalling in cancer
Babina, I. S., & Turner, N. C. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.8 · Cited by 799
Metadata
- Authors
- Trudel, S., Li, Z. H., Wei, E., Wiesmann, M., Chang, H., Chen, C., Reece, D., Heise, C., & Stewart, A. K.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-04-01
- Volume
- 105
- Issue
- 7
- Pages
- 2941-2948
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2088123597
- Cited by
- 289
- References
- 46
- FWCI
- 14.34
- Type
- journal article
- Language
- en
- Open access
- bronze
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. https://app.cochat.ai/papers/10.1182/blood-2004-10-3913
- The paper
- Trudel, S., Li, Z. H., Wei, E., Wiesmann, M., Chang, H., Chen, C., Reece, D., Heise, C., & Stewart, A. K. (2005). CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood. https://doi.org/10.1182/blood-2004-10-3913
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.
