QX77 Chemical Properties

Boiling point:

514.5±50.0 °C(Predicted)

Density 

1.32±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMF: 25mg/mL; DMF:PBS (pH 7.2) (1:2): 0.3mg/mL; DMSO: 15mg/mL

form 

A solid

pka

14?+-.0.70(Predicted)

color 

Light yellow to yellow

QX77 Usage And Synthesis

Uses

QX77 is a chaperone-mediated autophagy (CMA) activator and upregulates LAMP2A expression in vitro. QX77 induces Rab11 upregulation, rescues Rab11 down-regulation and trafficking deficiency in cystinotic cells[1]. QX77 can impede self-renewal and promote differentiation of ES cells[2].

Biological Activity

QX77 is a chaperone-mediated autophagy (CMA) activator derived from the atypical retinoid AR7 th at activates CMA by antagonizing retinoic acid receptor-α (RARα) signaling. QX77 rescues defective trafficking & lysosomal localization of the CMA receptor LAMP2A in cystinotic Ctns-/- MEFs and CTNS-KO human proximal tubule cells (PTCs) by restoring Rab11 expression and Rab11-positive vesicles trafficking to the level seen in wild-type cells (20 μM, 48 hrs). CMA activation by QX77 treatment (20 μM, 5 days) also significantly reduces toxic α-synuclein (α-syn) accumulation in PD patients iPSCs-derived astrocytes with LRRK2 G2019S mutation.

References

[1] Jinzhong Zhang, et al. Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A. J Biol Chem. 2017 Jun 23;292(25):10328-10346 DOI:10.1074/jbc.M116.764076
[2] Yi Xu, et al. Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells. Science. 2020 Jul 24;369(6502):397-403. DOI:10.1126/science.abb4467