388086-13-3

CAY10722 is an inhibitor of sirtuin 3 (SIRT3), a class III HDAC (71% inhibition at 200 μM).¹ SIRT3 is involved in modulating metabolic homeostasis as a NAD⁺-dependent protein deacetylase in the mitochondria. SIRT3 functions as either an oncogene or tumor suppressor, depending on cancer cell type.^2,3 High SIRT3 expression in patient-derived esophageal cancer tissues is associated with shorter survival and, in mice, downregulation leads to a lower tumor load.⁴ In contrast, low SIRT3 expression in patient-derived breast cancer cells is correlated with shorter survival.⁵

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1. Salo, H.S., Latinen, T., Poso, A., et al. Identification of novel SIRT3 inhibitor scaffolds by virtual screening Bioorg. Med. Chem. Lett. 23(10),2990-2995(2013).
2. Chen, Y., Fu, L., Wen, X., et al. Sirtuin-3 (SIRT3), a therapeutic target with oncogenic and tumor-suppressive function in cancer Cell Death Dis. 5(e1047),1-7(2014).
3. Xiong, Y., Wang, M., Zhao, J., et al. Sirtuin 3: A Janus face in cancer (Review) Int. J. Oncol. 49(6),2227-2235(2016).
4. Zhao, Y., Yang, H., Wang, X., et al. Sirtuin-3 (SIRT3) expression is associated with overall survival in esophageal cancer Ann. Diagn. Pathol. 17(6),483-485(2013).
5. Desouki, M.M., Doubinskaia, I., Gius, D., et al. Decreased mitochondrial SIRT3 expression is potential molecular biomarker associated with poor outcome in breast cancer Hum. Pathol. 45(5),1071–1077(2014).