QX77

QX77 (also known as CA77) is a novel, synthetic small-molecule activator of chaperone-mediated autophagy (CMA). Derived from the atypical retinoid AR7, QX77 acts as an antagonist of retinoic acid receptor-alpha (RARα). RARα normally functions as a transcriptional repressor of the CMA machinery; by antagonizing RARα and stabilizing its interaction with the co-repressor NCoR1, QX77 lifts this transcriptional brake. This leads to the upregulation of lysosome-associated membrane protein 2A (LAMP2A), the rate-limiting receptor for CMA substrate translocation, as well as Rab11, which facilitates LAMP2A trafficking to the lysosomal membrane. By selectively activating CMA, QX77 enhances the lysosomal degradation of damaged or misfolded proteins containing the KFERQ motif without affecting macroautophagy or proteasome pathways. It has demonstrated therapeutic potential in preclinical models of various conditions, including cystinosis, Parkinson's disease, diabetic retinopathy, and immune thrombocytopenia (ITP).

Other names

N-[4-(7-chloro-2H-1,4-benzoxazin-3-yl)phenyl]-acetamideN-[4-(7-chloro-2H-1,4-benzoxazin-3-yl)phenyl]acetamide