Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma.
Blood
; 117(4): 1311-4, 2011 Jan 27.
Article
in En
| MEDLINE
| ID: mdl-21081713
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.
Full text:
1
Database:
MEDLINE
Main subject:
Sulfonamides
/
Thiophenes
/
Protein Serine-Threonine Kinases
/
Cytotoxins
/
Protein Kinase Inhibitors
/
Endoribonucleases
/
Multiple Myeloma
Type of study:
Diagnostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Blood
Year:
2011
Type:
Article
Affiliation country:
United States