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.
QX77是一种分子伴侣介导的自噬 (Chaperone-mediated autophagy, CMA) 激活剂[1]。QX77可以激活分子伴侣介导的自噬改善细胞内运输缺陷[2]。QX77还可以减少细胞铁死亡，减缓氧化应激[3-4]。
在体外，QX77（5ng/ml）与20ng/mL MFG-E8同时干预TGF-β1处理的人胰腺星状细胞（HPSCs）24小时，QX77消除了MFG-E8对TGF-β1诱导的LAMP2A表达上调和MEF2D表达下降的抑制作用。QX77削弱了MFG-E8对氧化应激的缓解效果[3]。QX77（10μM）干预DDP（6μg/ml）处理的SKOV3/DDP细胞12。QX77提升了细胞活力，并影响了自噬相关蛋白的表达与定位[5]。
在体内，QX77（2.5mg/kg）在糖尿病大鼠模型建立第一天开始，每周一次玻璃体内注射，持续处理2周。QX77显著改善了糖尿病引起的视网膜生理功能损伤，降低了视网膜中ACSL4蛋白的表达、MDA水平以及有毒脂质过氧化产物4-HNE的积累，并减少了自噬体的数量，对早期糖尿病视网膜病变具有保护作用[4]。