Monepantel (AAD1566)是一种氨基乙腈衍生物类驱虫药，Monepantel可抑制mTOR/p70S6K信号通路诱导自噬。
Cas No.:887148-69-8
Sample solution is provided at 25 µL, 10mM.
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Monepantel (AAD1566) is an amino-acetonitrile derivative anthelmintic. Monepantel can inhibit the mTOR/p70S6K signaling pathway to induce autophagy[1-2]. Monepantel is applicable for research in gastrointestinal nematode infections, amyotrophic lateral sclerosis, and tumors[3-4].
In vitro, Monepantel (0-25µM) was applied to human ovarian cancer OVCAR-3 cells for 24-72 hours. Monepantel was able to induce autophagy by inhibiting mTOR phosphorylation and interfering with the mTOR/p70S6K signaling pathway[5]. Monepantel (25µM) was also used in various cancer cell lines, including MDA-MB-435, for 24-48 hours. Monepantel induced an endoplasmic reticulum stress response, upregulated the expression of ATF4, CHOP, and BiP proteins, activated the integrated stress response downstream, and leading to cell cycle arrest[6].
In vivo, Monepantel was administered via intraperitoneal injection (25 and 50mg/kg; three times a week; for 2 weeks) to female nude mice bearing subcutaneous OVCAR-3 ovarian cancer xenografts. Monepantel significantly inhibited tumor growth and reduced both tumor volume and weight[7]. In combination therapy, Monepantel, administered via intraperitoneal injection (25 or 50mg/kg; three times a week; for 2 weeks) along with pegylated liposomal doxorubicin (once a week) or gemcitabine (twice a week) to OVCAR-3 xenograft mice, significantly enhanced the inhibitory effect of the chemotherapeutic agents on tumor growth, induced tumor volume reduction, and demonstrated a synergistic inhibitory effect[8].
References:
[1] Food Safety Commission of Japan. Monepantel (Veterinary Medicinal Products). Food Saf (Tokyo). 2020 Mar 27;8(1):4-5.
[2] Mislang A, Mollard R, Tapia Rico G, et al. A preliminary assessment of oral monepantel's tolerability and pharmacokinetics in individuals with treatment-refractory solid tumors. Cancer Chemother Pharmacol. 2020 Nov;86(5):589-594.
[3] Bahrami F, Morris DL, Rufener L, et al. Anticancer properties of novel aminoacetonitrile derivative monepantel (ADD 1566) in pre-clinical models of human ovarian cancer. Am J Cancer Res. 2014 Sep 6;4(5):545-57.
[4] Canton C, Canton L, Lifschitz A, et al. Monepantel pharmaco-therapeutic evaluation in cattle: Pattern of efficacy against multidrug resistant nematodes. Int J Parasitol Drugs Drug Resist. 2021 Apr;15:162-167.
[5] Bahrami F, Pourgholami MH, Mekkawy AH, et al. Monepantel induces autophagy in human ovarian cancer cells through disruption of the mTOR/p70S6K signalling pathway. Am J Cancer Res. 2014 Sep 6;4(5):558-71.
[6] Harris TJ, Liao Y, Shi W, et al. Induction of endoplasmic reticulum stress is associated with the anti-tumor activity of monepantel across cancer types. Cancer Med. 2023 Jun;12(12):13522-13537.
[7] Bahrami F, Mekkawy AH, Badar S, et al. Monepantel antitumor activity is mediated through inhibition of major cell cycle and tumor growth signaling pathways. Am J Cancer Res. 2021 Jun 15;11(6):3098-3110.
[8] Ataie-Kachoie P, Pillai K, Badar S, et al. Monepantel considerably enhances the therapeutic potentials of PEGylated liposomal doxorubicin and gemcitabine in ovarian cancer: in vitro and in vivo studies. Am J Cancer Res. 2018 Oct 1;8(10):2064-2075.
Monepantel (AAD1566)是一种氨基乙腈衍生物类驱虫药，Monepantel可抑制mTOR/p70S6K信号通路诱导自噬[1-2]。Monepantel可用于胃肠道线虫感染、肌萎缩侧索硬化症和肿瘤等相关研究[3-4]。
在体外，Monepantel（0-25µM）处理人类卵巢癌OVCAR-3细胞24-72小时，Monepantel能够通过抑制mTOR磷酸化并干扰mTOR/p70S6K信号通路，从而诱导自噬[5]。Monepantel（25µM）在包括MDA‐MB‐435在内的多种癌症细胞系24-48小时。Monepantel能诱导内质网应激反应，上调ATF4、CHOP和BiP蛋白表达，激活下游的整合应激反应，导致细胞周期停滞[6]。
在体内，Monepantel以腹腔注射（25和50mg/kg；每周三次；持续2周）处理带有OVCAR-3卵巢癌皮下异种移植瘤的雌性裸鼠，Monepantel显著地抑制肿瘤生长，降低肿瘤体积和重量[7]。Monepantel以腹腔注射（25或50mg/kg；每周三次；持续2周）与聚乙二醇化脂质体多柔比星（每周一次）或吉西他滨（每周两次）联合使用处理OVCAR-3异种移植瘤小鼠，Monepantel能显著增强化疗药物对肿瘤生长的抑制效果，并诱导肿瘤体积缩小，且该抑制作用表现为协同效应[8]。
| Cell experiment [1]: | |
Cell lines | OVCAR-3 and A2780 cells (human ovarian cancer cell lines) |
Preparation Method | OVCAR-3 and A2780 cells were maintained in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum (FBS) at 37°C, 5% CO₂. Cells were treated with Monepantel at indicated concentrations (0-25μM) for 24, 48, and 72 hours. |
Reaction Conditions | 0-25μM; 24–72h. |
Applications | Monepantel induced autophagy in ovarian cancer cells, as evidenced by the formation of acidic vesicular organelles (AVOs), conversion of LC3B-I to LC3B-II, and accumulation of SQSTM1/p62. Monepantel suppressed the mTOR/p70S6K signaling pathway, indicated by inhibition of mTOR phosphorylation (Ser2448) and downstream targets p70S6K and 4E-BP1. Monepantel-induced cytotoxicity was caspase-independent, did not induce apoptosis, and pharmacological inhibition of autophagy enhanced cytotoxic effects. |
| Animal experiment [2]: | |
Animal models | BALB/c Nu/Nu nude mice bearing subcutaneous OVCAR-3 ovarian cancer xenografts |
Preparation Method | Mice bearing established tumors (volume ~100mm³) were intraperitoneally administered Monepantel three times a week for 2 weeks. Tumors and body weight were measured regularly. Mice were sacrificed at the end of the treatment period for tumor collection and analysis. |
Dosage form | 25 and 50mg/kg; i.p.; Three times weekly for 2 weeks. |
Applications | Monepantel administration led to a dose-dependent suppression of tumor growth, as evidenced by a significant reduction in both tumor volume and tumor weight compared to vehicle-treated controls. The treatment induced necrosis in tumor tissues and significantly inhibited key tumor signaling pathways, including the mTOR/p70S6K/4EBP1 pathway, and downregulated expression of proteins involved in cell cycle regulation (cyclin D1, cyclin E2, CDK2, phosphorylated Rb) and growth signaling (IGF-1R, c-MYC). The treatment was well-tolerated with no observable side effects or body weight loss. |
References: | |
| Cas No. | 887148-69-8 | SDF | |
| 别名 | AAD1566 | ||
| Canonical SMILES | O=C(N[C@@](C)(C#N)COC1=CC(C#N)=CC=C1C(F)(F)F)C2=CC=C(SC(F)(F)F)C=C2 | ||
| 分子式 | C20H13F6N3O2S | 分子量 | 473.39 |
| 溶解度 | DMSO : ≥ 100 mg/mL (211.24 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 | 2.1124 mL | 10.5621 mL | 21.1242 mL |
| 5 mM | 422.5 μL | 2.1124 mL | 4.2248 mL |
| 10 mM | 211.2 μL | 1.0562 mL | 2.1124 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % 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.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
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