BO-264
目录号 : GC39483
A TACC3 inhibitor
Cas No.:2408648-20-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
BO-264 is a transforming acidic coiled-coil containing protein 3 (TACC3) inhibitor.1 It binds to TACC3 in thermal shift and drug affinity responsive target stability (DARTS) assays and inhibits the growth of JIMT-1, HCC1954, MDA-MB-231, MDA-MB-436, and CAL-51 cancer cells (IC50s = 0.19, 0.16, 0.12, 0.13, and 0.36 ?M, respectively). BO-264 is cytotoxic to RT4 cells that endogenously express TACC3-FGFR3 fusion proteins (IC50 = 3.66 ?M). It induces mitotic arrest, apoptosis, and aberrant spindle formation and reduces centrosomal localization of TACC3 in JIMT-1 cells. BO-264 (25 mg/kg) reduces tumor volume and increases median survival in an EMT6 mouse xenograft model.
1.Akbulut, O., Lengerli, D., Saatci, O., et al.A highly potent TACC3 inhibitor as a novel anticancer drug candidateMol. Cancer Ther.19(6)1243-1254(2020)
| Cas No. | 2408648-20-2 | SDF | |
| Canonical SMILES | COC1=CC=C(C2=NOC(NC3=NC(N4CCOCC4)=NC=C3)=C2)C=C1 | ||
| 分子式 | C18H19N5O3 | 分子量 | 353.38 |
| 溶解度 | DMSO: 50 mg/mL (141.49 mM) | 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 | 2.8298 mL | 14.1491 mL | 28.2981 mL |
| 5 mM | 0.566 mL | 2.8298 mL | 5.6596 mL |
| 10 mM | 0.283 mL | 1.4149 mL | 2.8298 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
A Highly Potent TACC3 Inhibitor as a Novel Anticancer Drug Candidate
Mol Cancer Ther 2020 Jun;19(6):1243-1254.PMID:32217742DOI:10.1158/1535-7163.MCT-19-0957
TACC3, a transforming acidic coiled-coil (TACC) family member, is frequently upregulated in a broad spectrum of cancers, including breast cancer. It plays critical roles in protecting microtubule stability and centrosome integrity that is often dysregulated in cancers; therefore, making TACC3 a highly attractive therapeutic target. Here, we identified a new TACC3-targeting chemotype, BO-264, through the screening of in-house compound collection. Direct interaction between BO-264 and TACC3 was validated by using several biochemical methods, including drug affinity responsive target stability, cellular thermal shift assay, and isothermal titration calorimetry. BO-264 demonstrated superior antiproliferative activity to the two currently reported TACC3 inhibitors, especially in aggressive breast cancer subtypes, basal and HER2+, via spindle assembly checkpoint-dependent mitotic arrest, DNA damage, and apoptosis, while the cytotoxicity against normal breast cells was negligible. Furthermore, BO-264 significantly decreased centrosomal TACC3 during both mitosis and interphase. BO-264 displayed potent antiproliferative activity (∼90% have less than 1 μmol/L GI50 value) in the NCI-60 cell line panel compromising of nine different cancer types. Noteworthy, BO-264 significantly inhibited the growth of cells harboring FGFR3-TACC3 fusion, an oncogenic driver in diverse malignancies. Importantly, its oral administration significantly impaired tumor growth in immunocompromised and immunocompetent breast and colon cancer mouse models, and increased survival without any major toxicity. Finally, TACC3 expression has been identified as strong independent prognostic factor in breast cancer and strongly prognostic in several different cancers. Overall, we identified a novel and highly potent TACC3 inhibitor as a novel potential anticancer agent, inducing spindle abnormalities and mitotic cell death.