ARN3236

一种SIK2抑制剂（对SIK2的IC50值分别为21.63nM和6.63nM）；在RAW 264.7细胞中抑制TNF-α分泌（IC50≈2.5µM），并在3µM时减少巨噬细胞中CRTC3和HDAC4的磷酸化；抑制10种卵巢癌细胞系的生长（IC50值为0.8-2.6µM），并增强其中8种对紫杉醇的敏感性；在1µM时使SKOV3细胞周期停滞在G2/M期，并诱导细胞凋亡和四倍体化；在卵巢癌小鼠异种移植模型中，以每天60mg/kg的剂量与紫杉醇联合使用时，对减少肿瘤生长具有协同作用。An inhibitor of SIK2 (IC50 = 50s = 21.63 and 6.63 nM, respectively); inhibits TNF-α secretion in RAW 264.7 cells (IC50 = ~2.5 µM) and reduces phosphorylation of CRTC3 and HDAC4 in macrophages at 3 µM; inhibits growth of 10 ovarian cancer cell lines (IC50s = 0.8-2.6 µM) and increases sensitivity of eight of them to paclitaxel; halts the cell cycle at the G2/M phase and induces apoptosis and tetraploidy in SKOV3 cells at 1 µM; has an additive effect on reducing tumor growth when used in combination with paclitaxel in an ovarian cancer mouse xenograft model at 60 mg/kg per day.分子式C19H16N2O2S分子量336.4COC1=CC(OC)=C(C=C1)C2=CNC3=C2C(C4=CSC=C4)=CC=N3