QX77 is a chaperone-mediated autophagy (CMA) activator[1]. QX77 can activate CMA to ameliorate intracellular trafficking defects[2], and also reduce ferroptosis and alleviate oxidative stress[3-4].
In vitro, when human pancreatic stellate cells (HPSCs) treated with TGF-β1 were co-treated with QX77 (5ng/mL) and 20ng/mL MFG-E8 for 24 hours, QX77 eliminated the inhibitory effect of MFG-E8 on the TGF-β1-induced upregulation of LAMP2A expression and downregulation of MEF2D expression. QX77 attenuated the mitigating effect of MFG-E8 on oxidative stress[5]. In SKOV3/DDP cells treated with DDP (6μg/mL), intervention with QX77 (10μM) for 12 hours enhanced cell viability and affected the expression and localization of autophagy-related proteins[6].
In vivo, in a diabetic rat model, intravitreal injection of QX77 (2.5mg/kg) was administered once per week starting from the first day of model establishment for a duration of 2 weeks. QX77 significantly improved diabetes-induced impairment of retinal physiological function, reduced the expression of ACSL4 protein, decreased MDA levels and the accumulation of the toxic lipid peroxidation product 4-HNE in the retina, and reduced the number of autophagosomes, demonstrating a protective effect against early diabetic retinopathy[4].
References:
[1] Rahman F, Johnson JL, Ait Kbaich M, et al. Reconstitution of Rab11-FIP4 Expression Rescues Cellular Homeostasis in Cystinosis. Mol Cell Biol. 2024;44(12):577-589.
[2] Li J, Zeng S, Sun Y, et al. Gluconic acid alleviates hypertrophic scar formation through binding PLOD1, reducing p-AKT signaling and activating autophagy. Phytomedicine. 2025 Jul 25;143:156825.
[3] Liu C, Sun W, Zhu T, et al. Glia maturation factor-β induces ferroptosis by impairing chaperone-mediated autophagic degradation of ACSL4 in early diabetic retinopathy. Redox Biol. 2022 Jun;52:102292.
[4] Ren Y, Cui Q, Zhang J, et al. Z Milk Fat Globule-EGF Factor 8 Alleviates Pancreatic Fibrosis by Inhibiting ER Stress-Induced Chaperone-Mediated Autophagy in Mice. Front Pharmacol. 2021 Aug 5;12:707259.
[5] Du P, Xu X, Wang Y. Hsa_circ_0000585 promotes chemoresistance to cis-platin in epithelial cells of ovarian cancer by modulating autophagy. Biochem Biophys Res Commun. 2023 Oct 20;678:186-192.