BI 2536
(Synonyms: BI-2536;BI2536) 目录号 : GC12450
BI 2536是一种双重Polo样激酶（PLK）/溴结构域抑制剂，在无细胞激酶实验中，BI 2536 对PLK1、PLK2和PLK3的半数抑制浓度（IC50）值分别为0.83nM、3.5nM和9.0nM。
Cas No.:755038-02-9
Sample solution is provided at 25 µL, 10mM.
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BI 2536, dual Polo-like kinase (PLK)/bromodomain inhibitors, effectively reactivate latent HIV-1. Half maximal inhibitory concentration (IC50) values of BI 2536 against PLK1, PLK2, and PLK3 in cell-free kinase assays are 0.83nM, 3.5nM and 9.0nM, respectively[1].
In vitro, BI 2536 (0.1, 0.5, 1 and 2μM; 72h) inhibited the proliferation of ovarian cancer cells and induced cell cycle arrest at the G2/M phases[2]. BI 2536 (28.23 and 17.30nM; 24 and 48h) promotes neuroblastoma cell death via minichromosome maintenance complex components 2 and 10[3]. Alisertib cooperates with BI 2536 (14h and 24h) to induce cell cycle arrest and DNA double-strand breaks in small cell lung cancer[4]. BI 2536 (5nM and 10nM; 24h) induces apoptosis and attenuates the autophagic process in neuroblastoma cells[5].
In vivo, BI 2536 (10mg/kg/every other day; 20 days; i.p.) inhibited tumor growth in the cell-derived xenograft model mice[2]. Combining BI 2536 (10mg/kg; every other day for a total of five doses; i.v.) with alisertib impaired DNA repair capacity and significantly delayed tumor growth in mice[4].
References:
[1] Gohda J, Suzuki K, Liu K, et al. BI-2536 and BI-6727, dual Polo-like kinase/bromodomain inhibitors, effectively reactivate latent HIV-1. Sci Rep. 2018 Feb 23;8(1):3521.
[2] Huo J, Shen Y, Zhang Y, et al. BI 2536 induces gasdermin E-dependent pyroptosis in ovarian cancer. Front Oncol. 2022 Aug 9;12:963928.
[3] Hsieh CH, Yeh HN, Huang CT, et al. BI-2536 Promotes Neuroblastoma Cell Death via Minichromosome Maintenance Complex Components 2 and 10. Pharmaceuticals (Basel). 2021 Dec 28;15(1):37.
[4] Zhang J, Liu X, Hou P, et al. BRCA1 orchestrates the response to BI-2536 and its combination with alisertib in MYC-driven small cell lung cancer. Cell Death Dis. 2024 Jul 31;15(7):551.
[5] Li Z, Yang C, Li X, et al. The dual role of BI 2536, a small-molecule inhibitor that targets PLK1, in induction of apoptosis and attenuation of autophagy in neuroblastoma cells. J Cancer. 2020 Mar 5;11(11):3274-3287.
BI 2536是一种双重Polo样激酶（PLK）/溴结构域抑制剂，在无细胞激酶实验中，BI 2536 对PLK1、PLK2和PLK3的半数抑制浓度（IC50）值分别为0.83nM、3.5nM和9.0nM[1]。
在体外实验中，BI 2536（0.1, 0.5, 1和2μM; 72小时）抑制了卵巢癌细胞的增殖，并诱导细胞周期停滞在G2/M期[2]。BI-2536（28.23和17.30nM; 24和48小时）通过微染色体维持复合体组分2和10促进神经母细胞瘤细胞死亡[3]。阿利塞替布与BI 2536（14小时和24小时）协同作用，诱导小细胞肺癌细胞周期停滞和DNA双链断裂[4]。BI 2536（5nM和10nM; 24小时）诱导神经母细胞瘤细胞凋亡并减弱自噬过程[5]。
体内实验方面，BI 2536（10mg/kg/每隔一天; 20天; 腹腔注射）抑制了细胞来源的异种移植模型小鼠中的肿瘤生长[2]。将BI 2536（10mg/kg/每隔一天; 给药5次; 静脉注射）与阿利塞替布联合使用，可损害DNA修复能力，并显著延缓小鼠中肿瘤的生长[4]。
| Cell experiment [1]: | |
Cell lines | Human ovarian cell line A2780 cell |
Preparation Method | Cells were seeded in a 12-well plate and treated with indicated drugs (DMSO, 0.1μM, 0.5μM, 1.0μM and 2.0μM BI 2536) for 72h. Then cells were washed with PBS, harvested, and fixed with anhydrous ethanol overnight. After washed with PBS, PI/RNase staining was added to suspend cells and incubate for 30min in dark. The cell cycle distribution was determined by flow cytometry. |
Reaction Conditions | 0.1μM, 0.5μM, 1.0μM and 2.0μM; 72h |
Applications | BI 2536 inhibited the proliferation of ovarian cancer cells and induced cell cycle arrest at the G2/M phases. |
| Animal experiment [2]: | |
Animal models | Athymic nu/nu mice |
Preparation Method | A total of 5 × 106 SCLC cells, suspended in a 100μL volume, were mixed with an equal volume of Matrigel and inoculated into the dorsal flank of a 4-6 week-old nu/nu mice. Once the tumors became palpable and measurable, mice were randomized into four groups and treated with either DMSO control, BI 2536 alone, alisertib alone, or a combination of BI 2536 and alisertib. BI 2536 (10mg/kg) was administered via tail vein injection every other day for a total of five doses. Alisertib (20mg/kg) was given orally every other day for a total of five doses. Each animal was tracked individually every other day for tumor growth by external caliper measurements of the protruding subcutaneous tumors. The tumor size was calculated using the following formula: Volume = (length × width2)/2. |
Dosage form | 10mg/kg; every other day for a total of five doses; i.v. |
Applications | Combining BI 2536 with alisertib impaired DNA repair capacity and significantly delayed tumor growth in mice. |
References: | |
| Cas No. | 755038-02-9 | SDF | |
| 别名 | BI-2536;BI2536 | ||
| 化学名 | 4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide | ||
| Canonical SMILES | CCC1C(=O)N(C2=CN=C(N=C2N1C3CCCC3)NC4=C(C=C(C=C4)C(=O)NC5CCN(CC5)C)OC)C | ||
| 分子式 | C28H39N7O3 | 分子量 | 521.67 |
| 溶解度 | ≥ 13.04 mg/mL in DMSO, ≥ 92.4 mg/mL in EtOH with ultrasonic | 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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| 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 | 1.9169 mL | 9.5846 mL | 19.1692 mL |
| 5 mM | 0.3834 mL | 1.9169 mL | 3.8338 mL |
| 10 mM | 0.1917 mL | 0.9585 mL | 1.9169 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。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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