VX-680 (MK-0457,Tozasertib)
(Synonyms: 陶扎色替,VX 680; MK-0457) 目录号 : GC11549
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。
Cas No.:639089-54-6
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | Human umbilical vein endothelial cells (HUVEC) |
Preparation Method | Cells were cultured in 96‑well plates and treated for 24, 48, 72 and 96h with VX‑680 (0, 1.5 and 2.25µM). Cell viability was assessed by MTT assay. |
Reaction Conditions | 0, 1.5, 2.25µM; 24, 48, 72, 96h |
Applications | VX‑680 significantly inhibited HUVEC viability in a dose‑ and time‑dependent manner. |
| Animal experiment [2]: | |
Animal models | Female NOD/SCID mice |
Preparation Method | Mice were transplanted with NCI-H1299 and HCC827 cells, respectively, and tumor volume was measured twice weekly using calipers. VX-680 treatment was initiated when the average tumor volume reached 150-200mm3. Mice were assigned to different treatment groups. VX-680 was prepared from 50% PEG-300 in PBS. Each dose of VX-680 was administered using four xenograft mice transplanted with either of the two cell lines. Mice were intraperitoneally injected twice daily with 0, 5, 10, 20, 30, and 50mg/kg of VX-680.The experiments were terminated when the largest tumours reached 1500mm3. |
Dosage form | 0, 5, 10, 20, 30, 50mg/kg; i.p. |
Applications | NCI-H1299 was highly sensitive to VX-680 treatments, whereas HCC827 was not responsive at any dose. |
References: | |
| Cas No. | 639089-54-6 | SDF | |
| 别名 | 陶扎色替,VX 680; MK-0457 | ||
| 化学名 | N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide | ||
| Canonical SMILES | CC1=CC(=NN1)NC2=NC(=NC(=C2)N3CCN(CC3)C)SC4=CC=C(C=C4)NC(=O)C5CC5 | ||
| 分子式 | C23H28N8OS | 分子量 | 464.59 |
| 溶解度 | ≥ 23.25 mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1524 mL | 10.7622 mL | 21.5244 mL |
| 5 mM | 430.5 μL | 2.1524 mL | 4.3049 mL |
| 10 mM | 215.2 μL | 1.0762 mL | 2.1524 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: >99.50%
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