CA77.1

CA77.1 (CA) is a synthetic compound that activates chaperone-mediated autophagy (CMA) by increasing the expression of the lysosomal receptor for this pathway, LAMP2A, in lysosomes. CA77.1 is a derivative of earlier compound AR7(HY-101106), which shows potent CMA activation in vitro but is not suitable for in vivo use.[1][2][3] CA77.1 is able to activate CMA in vivo, and demonstrates brain penetrance and favorable pharmacokinetics. It has been shown in animal studies that in vivo administration of CA77.1 to enhance chaperone-mediated autophagy, may help to degrade toxic pathogenic protein products such as tau proteins and has potential applications in the treatment of Alzheimer's disease[4][5] particularly in improving both behavior and neuropathology in PS19 mice models.[6]

CA77.1
Solid
Identifiers
  • N-[4-(6-chloroquinoxalin-2-yl)phenyl]acetamide
PubChem CID
Chemical and physical data
FormulaC16H12ClN3O
Molar mass297.74 g·mol−1
3D model (JSmol)
  • CC(=O)NC1=CC=C(C=C1)C2=CN=C3C=C(C=CC3=N2)Cl
  • InChI=1S/C16H12ClN3O/c1-10(21)19-13-5-2-11(3-6-13)16-9-18-15-8-12(17)4-7-14(15)20-16/h2-9H,1H3,(H,19,21)
  • Key:ZQXMPDVGBWOTBY-UHFFFAOYSA-N

References
  1. Anguiano J, Garner TP, Mahalingam M, Das BC, Gavathiotis E, Cuervo AM (June 2013). "Chemical modulation of chaperone-mediated autophagy by retinoic acid derivatives". Nature Chemical Biology. 9 (6): 374–82. doi:10.1038/nchembio.1230. PMC 3661710. PMID 23584676.
  2. US 9512092, Cuervo AM, Gavathiotis E, Xin Q, Das BC, "Retinoic acid receptor antagonists as chaperone-mediated autophagy modulators and uses thereof", published 18 June 2015, assigned to Albert Einstein College of Medicine of Yeshiva
  3. WO 2020077024, Cuervo AM, Gavathiotis E, "Benzoxazole and related compounds useful as chaperone-mediated autophagy modulators", published 16 April 2020, assigned to Albert Einstein College of Medicine of Yeshiva
  4. Bourdenx M, Martín-Segura A, Scrivo A, Rodriguez-Navarro JA, Kaushik S, Tasset I, et al. (April 2021). "Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome". Cell. 184 (10): 2696–2714.e25. doi:10.1016/j.cell.2021.03.048. PMC 8152331. PMID 33891876.
  5. Cuervo AM, et al. Compounds Useful as Chaperone-Mediated Autophagy Modulators. Patent WO 2020/046335
  6. https://www.medchemexpress.com/ca77-1.html. {{cite web}}: Missing or empty |title= (help)


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