Home Immunology & Inflammation SIK inhibitor - Apoptosis related activator ARN-3236 For research use only.

ARN-3236

ARN-3236 is a potent, orally available and selective inhibitor of salt-inducible kinase 2 (SIK2) with IC50 of <1 nM, 21.63 nM and 6.63 nM for SIK2, SIK1 and SIK3, respectively. ARN-3236 induces apoptosis in cancer cells.

ARN-3236 Chemical Structure

ARN-3236 Chemical Structure

CAS No. 1613710-01-2

Purity & Quality Control

ARN-3236 Related Products

Biological Activity

Description ARN-3236 is a potent, orally available and selective inhibitor of salt-inducible kinase 2 (SIK2) with IC50 of <1 nM, 21.63 nM and 6.63 nM for SIK2, SIK1 and SIK3, respectively. ARN-3236 induces apoptosis in cancer cells.
Targets
SIK2 [1]
(Cell-free assay)		 SIK3 [1]
(Cell-free assay)		 SIK1 [1]
(Cell-free assay)
1 nM 6.63 nM 21.63 nM
In vitro
In vitro

SIK2 is overexpressed in approximately 30% of high grade serous ovarian cancers. ARN-3236 inhibits growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 μM, where the IC50 of ARN-3236 is inversely correlated with endogenous SIK2 expression (Pearson’s r = −0.642, P = 0.03). ARN-3236 enhances sensitivity to paclitaxel in 8 of 10 cell lines. In at least three cell lines a synergistic interaction is observed. ARN-3236 uncouples the centrosome from the nucleus in interphase, blocks centrosome separation in mitosis, causes prometaphase arrest and induces apoptotic cell death and tetraploidy. ARN-3236 also inhibits AKT phosphorylation and attenuates survivin expression.[2]
Cell Research Cell lines HEY, A2780, UPN251, OVCAR3, OVCAR5, OVCAR8, ES-2, OC316, SKOv3 and IGROV1
Concentrations 1 μM, 2 μM, 3 μM, 5 μM
Incubation Time 16 h, 24 h, 32 h, 48 h
Method

Cells are seeded in 96-well cell culture plates in triplicate and incubated for 16 hrs. Then cells are treated with DMSO or ARN-3236 for 24 hrs followed by an additional 72 hrs incubation with paclitaxel (PTX) at the concentration indicated.
In Vivo
In vivo

The antitumor activity of ARN-3236 is measured using ovarian cancer xenograft model in nu/nu mice. In SKOv3ip xenograft model, ARN-3236 plus paclitaxel produces greater inhibition of tumor growth than any other group and showed statistically significant difference compared to paclitaxel alone (P = 0.028). ARN-3236 also inhibits SIK2 activity and enhances paclitaxel sensitivity in OVCAR8 xenografts. [2]
Animal Research Animal Models Female athymic nu/nu mice injected SKOv3ip1 and OVCAR8 cells
Dosages 60 mg/kg
Administration Oral gavage

Chemical Information & Solubility

Molecular Weight 336.41 Formula

C19H16N2O2S
CAS No. 1613710-01-2 SDF --
Smiles COC1=CC(=C(C=C1)C2=CNC3=NC=CC(=C23)C4=CSC=C4)OC
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 67 mg/mL ( (199.16 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 7 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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