ARN-3236 是一种口服有活性的、具有选择性的盐诱导激酶2 (SIK2)抑制剂，它能够抑制SIK1 (IC50:21.63 nM)、SIK2(IC50<1 nM)和 SIK3(IC50:6.63 nM)。它具有抗肿瘤作用。

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.

Salt-inducible kinase 2 (SIK2) is overexpressed in approximately 30% of high-grade serous ovarian cancers.?ARN-3236 inhibited the growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 μmol/L, where the IC50 of ARN-3236 was inversely correlated with endogenous SIK2 expression (Pearson r = -0.642, P = 0.03).?ARN-3236 enhanced sensitivity to paclitaxel in 8 of 10 cell lines, as well as in SKOv3ip (P = 0.028) and OVCAR8 xenografts.?In at least three cell lines, a synergistic interaction was observed.?ARN-3236 uncoupled the centrosome from the nucleus in interphase, blocked centrosome separation in mitosis, caused prometaphase arrest, and induced apoptotic cell death and tetraploidy.?ARN-3236 also inhibited AKT phosphorylation and attenuated survivin expression.

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.

1613710-01-2

C19H16N2O2S

336.41

DMSO:130 mg/mL (386.43 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years