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Abl Protein-Tyrosine Kinase Inhibitor STI571 Inhibits In Vitro Signal Transduction Mediated by c-Kit and Platelet-Derived Growth Factor Receptors
Abstract
STI571 (formerly known as CGP 57148B) is a protein-tyrosine kinase inhibitor that is currently in clinical trials for the treatment of chronic myelogenous leukemia. STI571 selectively inhibits the Abl and platelet-derived growth factor (PDGF) receptor tyrosine kinases in vitro and blocks cellular proliferation and tumor growth of Bcr-abl- or v-abl-expressing cells. We have further investigated the profile of STI571 against related receptor tyrosine kinases. STI571 was found to potently inhibit the kinase activity of the alpha- and beta-PDGF receptors and the receptor for stem cell factor, but not the closely related c-Fms, Flt-3, Kdr, Flt-1, and Tek tyrosine kinases. Additionally, no inhibition of c-Met or nonreceptor tyrosine kinases such as Src and Jak-2 has been observed. In cell-based assays, STI571 selectively inhibited PDGF and stem cell factor-mediated cellular signaling, including ligand-stimulated receptor autophosphorylation, inositol phosphate formation, and mitogen-activated protein kinase activation and proliferation. These results expand the profile of STI571 and suggest that in addition to chronic myelogenous leukemia, STI571 may have clinical potential in the treatment of diseases that involve abnormal activation of c-Kit or PDGF receptor tyrosine kinases.
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Cited by
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Self-citationA quantitative analysis of kinase inhibitor selectivity
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Metadata
- Authors
- Buchdunger, E., Cioffi, C. L., Law, N., Stover, D., Ohno-Jones, S., Druker, B. J., & Lydon, N. B.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 295
- Issue
- 1
- Pages
- 139-145
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2151504205
- Cited by
- 1,274
- References
- 0
- FWCI
- 35.94
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Abl Protein-Tyrosine Kinase Inhibitor STI571 Inhibits In Vitro Signal Transduction Mediated by c-Kit and Platelet-Derived Growth Factor Receptors. https://app.cochat.ai/papers/10.1016/s0022-3565(24)38879-2
- The paper
- Buchdunger, E., Cioffi, C. L., Law, N., Stover, D., Ohno-Jones, S., Druker, B. J., & Lydon, N. B. (2000). Abl Protein-Tyrosine Kinase Inhibitor STI571 Inhibits In Vitro Signal Transduction Mediated by c-Kit and Platelet-Derived Growth Factor Receptors. The Journal of Pharmacology and Experimental Therapeutics. https://doi.org/10.1016/s0022-3565(24)38879-2
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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