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]。