Chad Anthony Dickey,Amirthaa Suntharalingam,Brian S. J. Blagg
申请号：
US14083031
公开号：
US09045434B1
申请日:
2013.11.18
申请国别(地区):
US
年份:
2015
代理人:
摘要：
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 molecule inhibitors. Grp94 contributes to the intracellular accumulation of mutant myocilin. Tailored treatments aimed at disrupting the Grp94/mutant myocilin interaction can be used as a new therapeutic strategy for myocilin glaucoma. The inventors developed a compound having a general backbone structure of geldanamycin (GDA) and radicicol (RDC) in which a more hydrophobic surrogate of the quinone in GDA is linked to the resorcinol in RDC through a cis-amide bioisostere.
