AZD1480
(Synonyms: 5-氯-N2-[(1S)-1-(5-氟-2-嘧啶基)乙基]-N4-(5-甲基-1H-吡唑-3-基)-2,4-嘧啶二胺,AZD 1480) 目录号 : GC12504
AZD1480是一种JAK抑制剂（JAK1：IC50 = 1.3nM；JAK2：IC50 = 0.4nM） 。
Cas No.:935666-88-9
Sample solution is provided at 25 µL, 10mM.
AZD1480 is a JAK inhibitor (JAK1: IC50 = 1.3nM; JAK2: IC50 = 0.4nM) [1]. AZD1480 exerts anti-tumor effects by blocking the JAK/STAT signaling pathway and is commonly used to treat solid tumors [2-3].
In LN-17 cells, cell viability was inhibited in a dose-dependent manner after AZD1480 (0.5μM, 1μM; 72h) treatment [4]. In U251-MG and U87-MG cells, AZD1480 (1μM; 72h) inhibits constitutive STAT-3 and JAK2 activation in glioma cells [5]. In NCI-N592 cells, AZD1480 (0.3μM, 1μM, 3μM; 48h) induces G2-M cell-cycle arrest and apoptosis [6]. In CWR22Rv1 cells, AZD1480 (0-400nM; 2h) effectively reduced both ligand-induced and constitutive activation of Stat5a/b in a dose-dependent manner [7].
In Renca cell subcutaneous tumor mice model, AZD1480 (50mg/kg; po; 14d) inhibits Renca tumor growth in vivo with a reduction in tumor myeloid cell infiltration [8]. In HEK293T cell xenograft mice model, AZD1480 (30mg/kg, 50mg/kg; po; 28d) reduces angiogenesis and significantly decreases tumor volume in mouse xenograft models [9]. In MO4 cell xenograft mice model, AZD1480 (30mg/kg; po; 7d) delays tumor growth in a melanoma model while enhancing the suppressive activity of myeloid-derived suppressor cells [10].
References:
[1]. Wang SW, Hu J, Guo QH, et al. AZD1480, a JAK inhibitor, inhibits cell growth and survival of colorectal cancer via modulating the JAK2/STAT3 signaling pathway. Oncology Reports. 2014 Nov; 32(5): 1991-1998.
[2]. Suryani S, Bracken LS, Harvey RC, et al. Evaluation of the in vitro and in vivo efficacy of the JAK inhibitor AZD1480 against JAK-mutated acute lymphoblastic leukemia. Molecular cancer therapeutics. 2015 Feb 1; 14(2): 364-374.
[3]. Plimack ER, LoRusso PM, McCoon P, et al. AZD1480: a phase I study of a novel JAK2 inhibitor in solid tumors. The oncologist. 2013 Jul 1; 18(7): 819-820.
[4]. Hedvat M, Huszar D, Herrmann A, et al. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer cell. 2009 Dec 8; 16(6): 487-497.
[5]. McFarland BC, Ma JY, Langford CP, et al. Therapeutic potential of AZD1480 for the treatment of human glioblastoma. Molecular cancer therapeutics. 2011 Dec 1;10(12): 2384-2393.
[6]. Lee JH, Park KS, Alberobello AT, et al. The Janus kinases inhibitor AZD1480 attenuates growth of small cell lung cancers in vitro and in vivo. Clinical Cancer Research. 2013 Dec 15; 19(24): 6777-6786.
[7]. Gu L, Liao Z, Hoang DT, et al. Pharmacologic Inhibition of Jak2–Stat5 Signaling By Jak2 Inhibitor AZD1480 Potently Suppresses Growth of Both Primary and Castrate-Resistant Prostate Cancer. Clinical Cancer Research. 2013 Oct 15; 19(20): 5658-5674.
[8]. Xin H, Herrmann A, Reckamp K, et al. Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480. Cancer research. 2011 Nov 1; 71(21): 6601-6610.
[9]. Murakami T, Takigawa N, Ninomiya T, et al. Effect of AZD1480 in an epidermal growth factor receptor-driven lung cancer model. Lung cancer. 2014 Jan 1; 83(1): 30-36.
[10]. Maenhout SK, Du Four S, Corthals J, et al. AZD1480 delays tumor growth in a melanoma model while enhancing the suppressive activity of myeloid-derived suppressor cells. Oncotarget. 2014 Jul 25; 5(16): 6801.
AZD1480是一种JAK抑制剂（JAK1：IC50 = 1.3nM；JAK2：IC50 = 0.4nM） [1]。AZD1480通过阻断JAK/STAT信号通路发挥抗肿瘤作用，常用于治疗实体瘤 [2-3]。
在LN-17细胞中，AZD1480（0.5μM、1μM；72h）处理后，细胞活力以剂量依赖性方式受到抑制 [4]。在U251-MG和U87-MG细胞中，AZD1480（1μM；72h）抑制神经胶质瘤细胞中的组成性STAT-3和JAK2活化 [5]。在NCI-N592细胞中，AZD1480（0.3μM、1μM、3μM；48h）诱导G2-M细胞周期阻滞和细胞凋亡 [6]。在CWR22Rv1细胞中，AZD1480（0-400nM；2h）以剂量依赖性方式有效降低Stat5a/b的配体诱导和组成性激活 [7]。
在Renca细胞皮下肿瘤小鼠模型中，AZD1480（50mg/kg；po；14d）可抑制Renca肿瘤体内生长，并减少肿瘤髓系细胞浸润 [8]。在HEK293T细胞异种移植小鼠模型中，AZD1480（30mg/kg、50mg/kg；po；28d）可减少血管生成，并显著减小小鼠异种移植模型中的肿瘤体积 [9]。在MO4细胞异种移植小鼠模型中，AZD1480（30mg/kg；po；7d）可延缓黑色素瘤模型中的肿瘤生长，同时增强髓系抑制细胞的抑制活性 [10]。
| Cell experiment [1]: | |
Cell lines | LN-17 cells |
Preparation Method | LN-17 cells (5 × 103) were plated in 96-well plates in quintuplicate in RPMI plus 10% charcoal-stripped FBS and allowed to attach for 24h prior to the addition of DMSO or AZD1480 to the culture medium. After 72h, 20μL/well of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium/phenazine ethosulfate solution was added. After incubation (1h, 37℃, 5% CO2 atmosphere), absorbance at 490nm was recorded by using an ELISA plate reader. |
Reaction Conditions | 0.5μM, 1μM; 72h |
Applications | After AZD1480 treatment, LN-17 cell viability was inhibited in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Renca cell subcutaneous tumor mice model |
Preparation Method | For subcutaneous tumor model, 2.5 × 106 Renca cells suspended in 100μL PBS were injected into the flank of nude mice, respectively. When average tumor volume reached approximately 100 to 150mm3, AZD1480 or vehicle was administered by oral gavage either once a day at the dose of 50mg/kg, as indicated. Tumor size was measured by caliper every other day. |
Dosage form | 50mg/kg; po; 14d |
Applications | AZD1480 inhibits Renca tumor growth in vivo with a reduction in tumor myeloid cell infiltration. |
References: | |
| Cas No. | 935666-88-9 | SDF | |
| 别名 | 5-氯-N2-[(1S)-1-(5-氟-2-嘧啶基)乙基]-N4-(5-甲基-1H-吡唑-3-基)-2,4-嘧啶二胺,AZD 1480 | ||
| 化学名 | 5-chloro-2-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-N-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine | ||
| Canonical SMILES | CC1=CC(=NN1)NC2=NC(=NC=C2Cl)NC(C)C3=NC=C(C=N3)F | ||
| 分子式 | C14H14ClFN8 | 分子量 | 348.77 |
| 溶解度 | ≥ 93.8 mg/mL in DMSO, ≥ 4.57 mg/mL in EtOH with ultrasonic and warming | 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 | 2.8672 mL | 14.3361 mL | 28.6722 mL |
| 5 mM | 0.5734 mL | 2.8672 mL | 5.7344 mL |
| 10 mM | 0.2867 mL | 1.4336 mL | 2.8672 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。
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Quality Control & SDS
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- Purity: >98.00%
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