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Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma

(2011) BLOOD. 117(4). p.1311-1314
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Abstract
Activation of the adaptive Ire1-XBP1 pathway has been identified in many solid tumors and hematologic malignancies, including multiple myeloma (MM). Here, we report the identification of STF-083010, a novel small-molecule inhibitor of Ire1. STF-083010 inhibited Ire1 endonuclease activity, without affecting its kinase activity, after endoplasmic reticulum stress both in vitro and in vivo. Treatment with STF-083010 showed significant antimy-eloma activity in model human MM xenografts. Similarly, STF-083010 was preferentially toxic to freshly isolated human CD138(+) MM cells compared with other similarly isolated cell populations. The identification of this novel Ire1 inhibitor supports the hypothesis that the Ire1-XBP1 axis is a promising target for anticancer therapy, especially in the context of MM.
Keywords
KINASE/ENDORIBONUCLEASE IRE1P, UNFOLDED PROTEIN RESPONSE, TUMOR-GROWTH, ACTIVATION, CELLS, REVEALS, PATHWAY

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Citation

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Chicago
Papandreou, Ioanna, Nicholas C Denko, Michael Olson, Heleen Van Melckebeke, Sofie Lust, Arvin Tam, David E Solow-Cordero, et al. 2011. “Identification of an Ire1alpha Endonuclease Specific Inhibitor with Cytotoxic Activity Against Human Multiple Myeloma.” Blood 117 (4): 1311–1314.
APA
Papandreou, I., Denko, N. C., Olson, M., Van Melckebeke, H., Lust, S., Tam, A., Solow-Cordero, D. E., et al. (2011). Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. BLOOD, 117(4), 1311–1314.
Vancouver
1.
Papandreou I, Denko NC, Olson M, Van Melckebeke H, Lust S, Tam A, et al. Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. BLOOD. 2011;117(4):1311–4.
MLA
Papandreou, Ioanna, Nicholas C Denko, Michael Olson, et al. “Identification of an Ire1alpha Endonuclease Specific Inhibitor with Cytotoxic Activity Against Human Multiple Myeloma.” BLOOD 117.4 (2011): 1311–1314. Print.
@article{2005652,
  abstract     = {Activation of the adaptive Ire1-XBP1 pathway has been identified in many solid tumors and hematologic malignancies, including multiple myeloma (MM). Here, we report the identification of STF-083010, a novel small-molecule inhibitor of Ire1. STF-083010 inhibited Ire1 endonuclease activity, without affecting its kinase activity, after endoplasmic reticulum stress both in vitro and in vivo. Treatment with STF-083010 showed significant antimy-eloma activity in model human MM xenografts. Similarly, STF-083010 was preferentially toxic to freshly isolated human CD138(+) MM cells compared with other similarly isolated cell populations. The identification of this novel Ire1 inhibitor supports the hypothesis that the Ire1-XBP1 axis is a promising target for anticancer therapy, especially in the context of MM.},
  author       = {Papandreou, Ioanna and Denko, Nicholas C and Olson, Michael and Van Melckebeke, Heleen and Lust, Sofie and Tam, Arvin and Solow-Cordero, David E and Bouley, Donna M and Offner, Fritz and Niwa, Maho and Koong, Albert C},
  issn         = {0006-4971},
  journal      = {BLOOD},
  keyword      = {KINASE/ENDORIBONUCLEASE IRE1P,UNFOLDED PROTEIN RESPONSE,TUMOR-GROWTH,ACTIVATION,CELLS,REVEALS,PATHWAY},
  language     = {eng},
  number       = {4},
  pages        = {1311--1314},
  title        = {Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma},
  url          = {http://dx.doi.org/10.1182/blood-2010-08-303099},
  volume       = {117},
  year         = {2011},
}

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