ARN-3236

製品コードS8543 バッチS854302

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C19H16N2O2S
分子量 336.41 CAS No. 1613710-01-2
Solubility (25°C)* 体外 DMSO 67 mg/mL (199.16 mM)
Ethanol 7 mg/mL (20.8 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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 this compound is inversely correlated with endogenous SIK2 expression (Pearson’s r = −0.642, P = 0.03). It enhances sensitivity to paclitaxel in 8 of 10 cell lines. In at least three cell lines a synergistic interaction is observed. This chemical uncouples the centrosome from the nucleus in interphase, blocks centrosome separation in mitosis, causes prometaphase arrest and induces apoptotic cell death and tetraploidy. It 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, this compound plus paclitaxel produces greater inhibition of tumor growth than any other group and showed statistically significant difference compared to paclitaxel alone (P = 0.028). It also inhibits SIK2 activity and enhances paclitaxel sensitivity in OVCAR8 xenografts. [2]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HEY, A2780, UPN251, OVCAR3, OVCAR5, OVCAR8, ES-2, OC316, SKOv3 and IGROV1
濃度 1 μM, 2 μM, 3 μM, 5 μM
反応時間 16 h, 24 h, 32 h, 48 h
実験の流れ

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.
動物実験 動物モデル Female athymic nu/nu mice injected SKOv3ip1 and OVCAR8 cells
投薬量 60 mg/kg
投与方法 Oral gavage

参考

  • https://pubmed.ncbi.nlm.nih.gov/26590148/
  • https://pubmed.ncbi.nlm.nih.gov/27678456/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

PTH stimulation of Rankl transcription is regulated by SIK2 and 3 and mediated by CRTC2 and 3 through action of protein phosphatases 1, 2, 4, and 5 [ J Biol Chem, 2025, 301(8):110434] PubMed: 40609791
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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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