ARN-3236

Catalog No.S8543 Batch:S854301

Technical Data

Formula	C₁₉H₁₆N₂O₂S
Molecular Weight	336.41	CAS No.	1613710-01-2
Solubility (25°C)*	In vitro	DMSO	67 mg/mL (199.16 mM)
		Ethanol	2 mg/mL (5.94 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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

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]

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]

Protocol (from reference)

Cell Assay:^{^[2]}	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.
Animal Study:^{^[2]}	Animal Models Female athymic nu/nu mice injected SKOv3ip1 and OVCAR8 cells Dosages 60 mg/kg Administration Oral gavage

Cell Assay:^{^[2]}

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.

Animal Study:^{^[2]}

Animal Models
Female athymic nu/nu mice injected SKOv3ip1 and OVCAR8 cells
Dosages
60 mg/kg
Administration
Oral gavage

References

Selleck's ARN-3236 has been cited by 2 publications

Targeting phosphorylation circuits on CREB and CRTCs as the strategy to prevent acquired skin hyperpigmentation [ Int J Biol Sci, 2024, 20(1):312-330]	PubMed: 38164184
SIK2 promotes ovarian cancer cell motility and metastasis by phosphorylating MYLK [ Mol Oncol, 2022, 16(13):2558-2574]	PubMed: 35278271

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