For research use only. Not for therapeutic Use.
ARN-3236（Cat No.:I002773） is a highly potent and orally available inhibitor of salt-inducible kinase 2 (SIK2). It exhibits remarkable selectivity, with IC50 values of less than 1nM, 21.63nM, and 6.63nM for SIK2, SIK1, and SIK3, respectively. This selective inhibition of SIK2 activity has shown the ability to induce apoptosis in cancer cells. With its promising anti-cancer properties, ARN-3236 holds potential as a therapeutic agent for the treatment of cancer, particularly by targeting SIK2-mediated pathways involved in cell survival and proliferation.
| Catalog Number | I002773 |
| CAS Number | 1613710-01-2 |
| Synonyms | ARN-3236; ARN 3236; ARN3236.;3-(2,4-Dimethoxyphenyl)-4-(3-thienyl)-1H-pyrrolo[2,3-b]pyridine |
| Molecular Formula | C19H16N2O2S |
| Purity | ≥95% |
| Target | Salt-inducible Kinase (SIK) |
| Solubility | Soluble in DMSO |
| Storage | Store at -20°C |
| IUPAC Name | 3-(2,4-dimethoxyphenyl)-4-thiophen-3-yl-1H-pyrrolo[2,3-b]pyridine |
| InChI | InChI=1S/C19H16N2O2S/c1-22-13-3-4-15(17(9-13)23-2)16-10-21-19-18(16)14(5-7-20-19)12-6-8-24-11-12/h3-11H,1-2H3,(H,20,21) |
| InChIKey | WEHOIIGXTMKVRG-UHFFFAOYSA-N |
| SMILES | COC1=CC(=C(C=C1)C2=CNC3=NC=CC(=C23)C4=CSC=C4)OC |
| Reference | 1:Clin Cancer Res. 2017 Apr 15;23(8):1945-1954. doi: 10.1158/1078-0432.CCR-16-1562. Epub 2016 Sep 27. A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts to Paclitaxel.Zhou J,Alfraidi A,Zhang S,Santiago-O/’Farrill JM,Yerramreddy Reddy VK,Alsaadi A,Ahmed AA,Yang H,Liu J,Mao W,Wang Y,Takemori H,Vankayalapati H,Lu Z,Bast RC Jr, PMID: 27678456 PMCID: PMC5436602 [Available on 2018-04-15] DOI: 10.1158/1078-0432.CCR-16-1562 </br><span>Abstract:</span> Purpose: Salt-inducible kinase 2 (SIK2) is a centrosome kinase required for mitotic spindle formation and a potential target for ovarian cancer therapy. Here, we examine the effects of a novel small-molecule SIK2 inhibitor, ARN-3236, on sensitivity to paclitaxel in ovarian cancer.Experimental Design: 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.Results: 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.Conclusions: ARN-3236 is the first orally available inhibitor of SIK2 to be evaluated against ovarian cancer in preclinical models and shows promise in inhibiting ovarian cancer growth and enhancing paclitaxel chemosensitivity. Clin Cancer Res; 23(8); 1945-54. ©2016 AACR.©2016 American Association for Cancer Research. |
