ARN-3236

Catalog No.S8543 Batch:S854301

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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.)

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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

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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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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