ARN-3236 is an oral active and selective inhibitor of salt-inducible kinase 2 (SIK2), (SIK2, SIK1 and SIK3 with IC50s of <1 nM, 21.63 nM and 6.63 nM respectively). ARN-3236 Has anti-cancer activity.

SIK1:21.63 nM , SIK2:<1 nM , SIK3:6.63.nM

Salt-inducible kinase 2 (SIK2) 在约30%的高级浆液性卵巢癌中过表达。ARN-3236在10株卵巢癌细胞系中抑制其生长，IC50范围为0.8至2.6 μmol/L，且ARN-3236的IC50与内源性SIK2表达呈负相关（Pearson r = -0.642, P = 0.03）。ARN-3236还增强了8/10细胞系以及SKOv3ip（P = 0.028）和OVCAR8异种移植瘤对紫杉醇的敏感性。至少在三个细胞系中观察到了协同作用。ARN-3236在间期中断核与中心体的连接，在有丝分裂中阻止中心体分离，导致前期停滞，引发凋亡性细胞死亡和四倍体形成。ARN-3236还抑制了AKT磷酸化并减弱了生存蛋白表达。

SIK2 expression was determined in ovarian cancer tissue samples and cell lines.?ARN-3236 was tested for its efficiency to inhibit growth and enhance paclitaxel sensitivity in cultures and xenografts of ovarian cancer cell lines.?SIK2 siRNA and ARN-3236 were compared for their ability to produce nuclear-centrosome dissociation, inhibit centrosome splitting, block mitotic progression, induce tetraploidy, trigger apoptotic cell death and reduce AKT/survivin signaling.