CA77.1

CA77.1
Identifiers
	IUPAC name N-[4-(6-chloroquinoxalin-2-yl)phenyl]acetamide;
CAS Number	2412270-22-3 [ChemSpider];
PubChem CID	146439211;
ChemSpider	114641988;
CompTox Dashboard (EPA)	DTXSID701336851 ;
Chemical and physical data
Formula	C16H12ClN3O
Molar mass	297.74 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(=O)NC1=CC=C(C=C1)C2=CN=C3C=C(C=CC3=N2)Cl;
	InChI 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

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

This pharmacology-related article is a stub. You can help Wikipedia by expanding it.

[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

[Bourdenx_2021-4] 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.

[1]

[2]

[3]

[4]

[5]