EX 527 (SEN0014196),49843-98-3,IC-0235679

EX 527, as a SIRT1-selective inhibitor, inhibits Sirt1 ～100-fold more potently than Sirt2 and Sirt3 and has no effect on Sirt5′s deacetylation activit.The IC50 values for Sirt1 and Sirt3 are 0.09 ± 0.03 μM and 22.4 ± 2.7 μM, respectively. Sir2Tm was also efficiently inhibited by Ex-527 with IC50 of 0.9 ± 0.3 μM.[1]

In vitro experiment it shown that cell viability significantly increased and cell death decreased in cancer cells with SIRT1 silencing or?EX 527 (10 μM) treatment compared with the control after exposure to RSL3 or sulfasalazine.[2] In vitro, treatment with 1?μM EX-527 decreased colony formation of ovarian carcinoma cells, with or without overexpression of SIRT172. However, at 600?nM, EX-527 suppressed cell migration and inhibited the occurrence of epithelial–mesenchymal transition (EMT) in chemotherapy resistant oesophageal cancer cells.[4] In vitro experiment it indicated that SIRT 1 inhibition by?EX 527 (10 μM) elevated ROS production. SIRT1 and PGC-1α levels were dramatically decreased.[6]

In vivo efficacy test indicated that pharmacological blockade of Sirt-1 with 2 mg/kg EX 527/mouse/day daily for 3 weeks alleviated GVHD without impairing T-cell-mediated GVL activity.[3] In vivo efficacy study demonstrated that treatment with 5?mg/kg?EX 527 intraperitoneally in C57BL/6J mice abolished the protective effects of melatonin.[4] In vivo, the data indicated that LPS-induced intrapulmonary inflammation and LPS-induced elevation of 4E-BP1 phosphorylation were attenuated by?EX 527 (10?mg/kg, i.p.).[5]