AZD1152 is a highly selective Aurora B kinase (AURKB) inhibitor with an IC50 value of 0.37nM[1]. AZD1152 is a prodrug that is converted in vivo to its active form, AZD1152-hydroxyquinazoline pyrazol anilide (AZD1152-hQPA), and is primarily used for research and treatment of malignant tumors such as acute myeloid leukemia[2]. AZD1152 inhibits Aurora B kinase activity by competitively binding to its ATP binding site, affecting histone H3 phosphorylation, spindle assembly, and cytokinesis, thus inducing apoptosis and inhibiting tumor cell proliferation[3].
In vivo, AZD1152 (5, 25mg/kg) administered intraperitoneally to mice with MOLM13 cell xenograft tumors inhibited tumor growth. Furthermore, combination treatment with AZD1152 and vincristine or daunorubicin enhanced their anti-tumor effects[4]. AZD1152 (50, 100mg/kg) administered intraperitoneally to mice with H841 cell xenograft tumors for 10 days inhibited tumor growth and induced tumor regression[5]. AZD1152 (35mg/kg) administered intraperitoneally to mice with a colorectal cancer model for 4 days enhanced the cytotoxic effect of 8 Gy radiation on tumor cells[6].
References:
[1] Yang J, Ikezoe T, Nishioka C, et al. AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo[J]. Blood, The Journal of the American Society of Hematology, 2007, 110(6): 2034-2040.
[2] Aihara A, Tanaka S, Yasen M, et al. The selective Aurora B kinase inhibitor AZD1152 as a novel treatment for hepatocellular carcinoma[J]. Journal of hepatology, 2010, 52(1): 63-71.
[3] Borah N A, Reddy M M. Aurora kinase B inhibition: a potential therapeutic strategy for cancer[J]. Molecules, 2021, 26(7): 1981.
[4] Wilkinson R W, Odedra R, Heaton S P, et al. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis[J]. Clinical cancer research, 2007, 13(12): 3682-3688.
[5] Helfrich B A, Kim J, Gao D, et al. Barasertib (AZD1152), a small molecule Aurora B inhibitor, inhibits the growth of SCLC cell lines in vitro and in vivo[J]. Molecular cancer therapeutics, 2016, 15(10): 2314-2322.
[6] Tao Y, Leteur C, Calderaro J, et al. The aurora B kinase inhibitor AZD1152 sensitizes cancer cells to fractionated irradiation and induces mitotic catastrophe[J]. Cell Cycle, 2009, 8(19): 3172-3181.
AZD1152是一种高度选择性的Aurora B激酶（AURKB）抑制剂，IC50值为0.37nM[1]。AZD1152是一种前体药物，在体内转化为活性形式AZD1152-hydroxyquinazoline pyrazol anilide（AZD1152-hQPA），主要用于研究与治疗急性髓系白血病等恶性肿瘤[2]。AZD1152能够通过竞争性地结合Aurora B激酶的ATP结合位点抑制其活性，影响组蛋白H3磷酸化、纺锤体组装和胞质分裂，从而诱导肿瘤细胞凋亡并抑制其增殖[3]。
在体内，AZD1152（5, 25mg/kg）通过腹腔注射治疗MOLM13细胞异种移植小鼠，抑制了小鼠体内肿瘤的生长，AZD1152与长春新碱或柔红霉素联合使用还增强了它们的抗肿瘤能力[4]。AZD1152（50, 100mg/kg）通过腹腔注射治疗H841细胞异种移植小鼠10天，抑制了小鼠体内肿瘤的生长，引起了肿瘤消退[5]。AZD1152（35mg/kg）通过腹腔注射治疗结肠癌模型小鼠4天，增强了8Gy辐射对肿瘤细胞的杀伤作用[6]。