1380296-84-3Relevant academic research and scientific papers
Development of a Grp94 inhibitor
Duerfeldt, Adam S.,Peterson, Laura B.,Maynard, Jason C.,Ng, Chun Leung,Eletto, Davide,Ostrovsky, Olga,Shinogle, Heather E.,Moore, David S.,Argon, Yair,Nicchitta, Christopher V.,Blagg, Brian S. J.
, p. 9796 - 9804 (2012)
Heat shock protein 90 (Hsp90) represents a promising therapeutic target for the treatment of cancer and other diseases. Unfortunately, results from clinical trials have been disappointing as off-target effects and toxicities have been observed. These detriments may be a consequence of pan-Hsp90 inhibition, as all clinically evaluated Hsp90 inhibitors simultaneously disrupt all four human Hsp90 isoforms. Using a structure-based approach, we designed an inhibitor of Grp94, the ER-resident Hsp90. The effect manifested by compound 2 on several Grp94 and Hsp90α/β (cytosolic isoforms) clients were investigated. Compound 2 prevented intracellular trafficking of the Toll receptor, inhibited the secretion of IGF-II, affected the conformation of Grp94, and suppressed Drosophila larval growth, all Grp94-dependent processes. In contrast, compound 2 had no effect on cell viability or cytosolic Hsp90α/β client proteins at similar concentrations. The design, synthesis, and evaluation of 2 are described herein.
Compositions and methods of treatment for myocilin glaucoma by selectively inhibiting GRP94
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Paragraph 0072; 0073, (2015/06/09)
A compound and method for treating myocilin glaucoma using a selective Grp94 inhibitor is presented. Clearance of mutant myocilin can be promoted by selectively targeting the endoplasmic reticulum (ER) chaperone Grp94 using siRNA knockdown or small molecu
