CA77.1

Last updated
CA77.1
CA77-1 structure.png
Identifiers
  • N-[4-(6-chloroquinoxalin-2-yl)phenyl]acetamide
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
Formula C16H12ClN3O
Molar mass 297.74 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

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.

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. ↑ "WIPO - Search International and National Patent Collections". patentscope.wipo.int.


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