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Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma BLOOD Papandreou, I., Denko, N. C., Olson, M., Van Melckebeke, H., Lust, S., Tam, A., Solow-Cordero, D. E., Bouley, D. M., Offner, F., Niwa, M., Koong, A. C. 2011; 117 (4): 1311-1314

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 antimyeloma 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.

View details for DOI 10.1182/blood-2010-08-303099

View details for Web of Science ID 000286623400029

View details for PubMedID 21081713