VX-680 (MK-0457,Tozasertib) is a potent Aurora kinase inhibitor with Ki values of 0.6, 18, and 4.6nM for Aurora A/B/C, respectively, exhibiting anticancer activity[1, 2]. VX-680 has achieved tumor regression in acute myeloid leukemia (AML), pancreatic cancer, and colon cancer[1]. VX-680 also has anti-angiogenic effects[3].
In vitro, treatment of human umbilical vein endothelial cells (HUVECs) with VX-680 (0, 1.5, 2.25µM) for 24-96 h inhibited cell viability, reduced cell clone size and number, induced apoptosis, and inhibited cell migration in a dose- and time-dependent manner[4]. VX-680 (1-500nM) treatment of human adrenocortical carcinoma cells (SW13 cells) for 24-72h inhibited cell viability in a dose- and time-dependent manner, increasing G2/M phase cells and decreasing G1 phase cells[5].
In vivo, VX-680 (0-50mg/kg) administered intraperitoneally to mice xenografted with NCI-H1299 and HCC827 cells significantly inhibited the growth of NCI-H1299 xenografts, but had no effect on HCC827 xenografts[6].
References:
[1] Harrington E A, Bebbington D, Moore J, et al. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo[J]. Nature medicine, 2004, 10(3): 262-267.
[2] Li Y, Zhang Z F, Chen J, et al. VX680/MK-0457, a potent and selective Aurora kinase inhibitor, targets both tumor and endothelial cells in clear cell renal cell carcinoma[J]. American journal of translational research, 2010, 2(3): 296.
[3] Tran T H T, Vu L D B, Nguyen H Q, et al. Dual roles of oxostephanine as an Aurora kinase inhibitor and angiogenesis suppressor[J]. International Journal of Molecular Medicine, 2022, 50(5): 133.
[4] Sun X, Niu S, Zhang Z, et al. Aurora kinase inhibitor VX-680 suppresses the proliferation and migration of HUVECs and angiogenesis[J]. Molecular Medicine Reports, 2019, 19(5): 3841-3847.
[5] Pezzani R, Rubin B, Bertazza L, et al. The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line[J]. Investigational new drugs, 2016, 34(5): 531-540.
[6] Tagal V, Wei S, Zhang W, et al. SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers[J]. Nature communications, 2017, 8(1): 14098.
VX-680 (MK-0457,Tozasertib)是一种有效的Aurora激酶抑制剂，对Aurora A/B/C的Ki值分别为0.6、18、4.6nM，具有抗癌活性[1, 2]。VX-680在急性髓系白血病（AML）、胰腺癌和结肠癌中，均实现了肿瘤消退[1]。VX-680具有抗血管生成作用[3]。
在体外，VX-680（0, 1.5, 2.25µM）处理人脐静脉内皮细胞（HUVECs）24-96h， 以剂量和时间依赖性方式抑制了细胞活力，降低了细胞克隆的大小和数量，诱导了细胞凋亡，抑制了细胞迁移[4]。VX-680（1-500nM）处理人肾上腺皮质癌细胞（SW13细胞）24-72h，以剂量和时间依赖性方式抑制了细胞活力，增加了G2/M期细胞，减少了G1期细胞[5]。
在体内，VX-680（0-50mg/kg）通过腹腔注射分别治疗NCI-H1299细胞和HCC827细胞异种移植小鼠，显著抑制了NCI-H1299移植瘤的生长，但对HCC827移植瘤没有作用[6]。