ARN-3236是一种选择性盐诱导激酶2（SIK2）抑制剂（IC50<1nM）。ARN-3236也可抑制SIK1（IC50<21.63nM）和SIK3（IC50<6.63nM）的活性。
Cas No.:1613710-01-2
Sample solution is provided at 25 µL, 10mM.
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ARN-3236 is a selective salt-inducible kinase 2 (SIK2) inhibitor with an IC50 of less than 1nM. ARN-3236 also inhibits the activity of SIK1 (IC50<21.63nM) and SIK3 (IC50<6.63nM)[1-2]. By inhibiting SIK2 activity, ARN-3236 blocks centrosome separation, induces cell cycle arrest and apoptosis. ARN-3236 is used in research related to cancer and neuroprotection[3-4].
In vitro, colorectal cancer cells were pretreated with ARN-3236 (5–10µM) for 24 hours and subsequently irradiated with X-rays (2–6Gy). ARN-3236 significantly enhanced cellular radiosensitivity and increased radiation-induced growth inhibition and apoptosis. ARN-3236 dose-dependently reduced the efficiency of homologous recombination repair by inhibiting SIK2 kinase activity[5]. SKOv3, OVCAR8, and other ovarian cancer cells were pretreated with ARN-3236 (0.6–2µM) for 24 hours, followed by treatment with paclitaxel (0–25µM) for 72 hours. By inhibiting SIK2 kinase activity, ARN-3236 blocked centrosome separation and attenuated the AKT/survivin signaling pathway, thereby significantly enhancing the cytotoxicity of paclitaxel while inducing G2/M phase arrest and apoptosis[6].
In vivo, a pulmonary fibrosis model was established in BALB/C mice via intratracheal instillation of bleomycin (5 mg/kg). Starting on the day of modeling, the mice received a daily intraperitoneal injection of ARN-3236 (10–3mg/kg) for 28 days. ARN-3236 dose-dependently alleviated bleomycin-induced body weight loss and increased lung coefficient. ARN-3236 reduced hydroxyproline content, collagen deposition, and the expression of α-smooth muscle actin (α-SMA) and type I collagen (COL1A) in lung tissue, thereby significantly mitigating bleomycin-induced pulmonary fibrosis[7]. A depression model was induced in C57BL/6J mice using chronic social defeat stress (CSDS) or chronic unpredictable mild stress (CUMS). Starting at the end of the stress induction, the mice received a daily intraperitoneal injection of ARN-3236 (10–60mg/kg) for 2 weeks. ARN-3236 ameliorated CSDS-induced social avoidance behavior and produced significant antidepressant-like effects[8].
References:
[1] Lombardi MS, Gilliéron C, Dietrich D, et al. SIK inhibition in human myeloid cells modulates TLR and IL-1R signaling and induces an anti-inflammatory phenotype. J Leukoc Biol. 2016 May;99(5):711-21.
[2] Bon H, Wadhwa K, Schreiner A, et al. Salt-inducible kinase 2 regulates mitotic progression and transcription in prostate cancer. Mol Cancer Res. 2015 Apr;13(4):620-635.
[3] Rong Z, Zhang L, Li Z, et al. SIK2 maintains breast cancer stemness by phosphorylating LRP6 and activating Wnt/β-catenin signaling. Oncogene. 2022 Apr;41(16):2390-2403.
[4] Fang N, Wang Y, Chen Y, et al. SIK2 mediated mitochondrial homeostasis in spinal cord injury: modulating oxidative stress and the AIM2 inflammasome via CRTC1/CREB signaling. J Neuroinflammation. 2025 Dec 3;22(1):283.
[5] Meng Y, Li S, Lu DS, et al. Salt-inducible kinase 2 confers radioresistance in colorectal cancer by facilitating homologous recombination repair. MedComm (2020). 2025 Jan 28;6(2):e70083.
[6] Zhou J, Alfraidi A, Zhang S, et al. A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts to Paclitaxel. Clin Cancer Res. 2017 Apr 15;23(8):1945-1954.
[7] Zou L, Hong D, Li K, et al. Salt-inducible kinase 2 (SIK2) inhibitor ARN-3236 attenuates bleomycin-induced pulmonary fibrosis in mice. BMC Pulm Med. 2022 Apr 11;22(1):140.
[8] Liu Y, Tang W, Ji C, et al, The Selective SIK2 Inhibitor ARN-3236 Produces Strong Antidepressant-Like Efficacy in Mice via the Hippocampal CRTC1-CREB-BDNF Pathway. Front Pharmacol. 2021 Jan 14;11:624429.
ARN-3236是一种选择性盐诱导激酶2（SIK2）抑制剂（IC50<1nM）。ARN-3236也可抑制SIK1（IC50<21.63nM）和SIK3（IC50<6.63nM）的活性[1-2]。ARN-3236通过抑制SIK2活性来阻断中心体分离、诱导细胞周期停滞和凋亡。ARN-3236 6可用于癌症以及神经保护的相关研究[3-4]。
在体外，ARN-3236（5–10µM）预处理结直肠癌细胞24小时，随后进行X射线（2–6Gy）照射。ARN-3236可显著增强细胞的放射敏感性，同时增加辐射诱导的生长抑制和凋亡。ARN-3236通过抑制SIK2激酶活性，剂量依赖性地降低同源重组修复效率[5]。ARN-3236（0.6–2µM）预处理SKOv3、OVCAR8等卵巢癌细胞24小时，随后以紫杉醇（0–25µM）处理72小时。ARN-3236通过抑制SIK2激酶活性，阻断中心体分离并减弱AKT/survivin信号通路，显著增强紫杉醇的细胞毒性，同时诱导G2/M期阻滞、凋亡[6]。
在体内，ARN-3236（10–30mg/kg）每天一次腹腔注射，用于处理经博来霉素（5mg/kg）诱导的肺纤维化模型BALB/C小鼠，从造模当天开始持续28天。ARN-3236剂量依赖性地减轻了博来霉素引起的体重下降和肺系数升高，减少了肺组织中羟脯氨酸含量、胶原沉积以及α-平滑肌动蛋白（α-SMA）和I型胶原（COL1A）的表达，显著减轻了博来霉素诱导的肺纤维化[7]。ARN-3236（10–60mg/kg）每天一次腹腔注射，用于处理经慢性社交挫败应激（CSDS）或慢性不可预知温和应激（CUMS）诱导的抑郁模型C57BL/6J小鼠，从应激造模结束后开始持续2周。ARN-3236改善了CSDS引起的社交回避行为，产生了显著的抗抑郁样作用[8]。
| Cell experiment [1]: | |
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Cell lines |
SKOv3, OVCAR8, A2780, HEY, OVCAR3, OVCAR5, OC316, ES-2, IGROV1, UPN251 (human ovarian cancer cell lines) |
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Preparation Method |
Cells were seeded in 96-well plates and incubated for 16 hours. Cells were then pretreated with DMSO or ARN-3236 for 24 hours, followed by an additional 72 hours incubation with paclitaxel (PTX) at indicated concentrations. Cell viability was measured using the sulforhodamine B (SRB) assay. For mechanistic studies, cells were treated with ARN-3236 (0.6–2μM) alone, and then processed for immunostaining, cell cycle, apoptosis, or western blot analysis. |
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Reaction Conditions |
0.6–2μM; 24-72h. |
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Applications |
ARN-3236 inhibited ovarian cancer cell growth and synergistically enhanced sensitivity to paclitaxel in 8 out of 10 cell lines. ARN-3236 induced nuclear-centrosome uncoupling in interphase, blocked centrosome separation in mitosis, caused prometaphase arrest, and led to G2/M cell cycle arrest, apoptosis, and tetraploidy. ARN-3236 also inhibited AKT phosphorylation (at Ser473 and Thr308) and attenuated survivin expression. |
| Animal experiment [2]: | |
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Animal models |
BALB/C male mice |
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Preparation Method |
A pulmonary fibrosis model was established by intratracheal instillation of bleomycin (BLM, 5mg/kg in 100μL PBS) on day 0. Mice were then intraperitoneally (i.p.) administered ARN-3236 (10mg/kg and 30mg/kg) or vehicle once daily, starting from the day of BLM instillation. Lung tissues were harvested 28 days after BLM instillation for histological analysis, hydroxyproline assay, and molecular analysis. |
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Dosage form |
10mg/kg and 30mg/kg; i.p.; Once daily for 28 days. |
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Applications |
ARN-3236 treatment dose-dependently attenuated bleomycin-induced pulmonary fibrosis in mice. ARN-3236 partly reversed BLM-induced body weight loss and increased lung coefficient, reduced hydroxyproline content in lung tissues, decreased fibrotic scarring and collagen deposition, and suppressed the expression of fibrotic markers α-SMA and COL1A. |
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References: |
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| Cas No. | 1613710-01-2 | SDF | |
| 别名 | 3-(2,4-二甲氧基苯基)-4-(3-噻吩基)-1H-吡咯并[2,3-B]吡啶 | ||
| Canonical SMILES | COC1=CC=C(C2=CNC3=NC=CC(C4=CSC=C4)=C32)C(OC)=C1 | ||
| 分子式 | C19H16N2O2S | 分子量 | 336.41 |
| 溶解度 | DMSO : 130 mg/mL (386.43 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9726 mL | 14.8628 mL | 29.7256 mL |
| 5 mM | 594.5 μL | 2.9726 mL | 5.9451 mL |
| 10 mM | 297.3 μL | 1.4863 mL | 2.9726 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
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