BI 2536
(Synonyms: BI-2536;BI2536) 目录号 : GC12450
A potent inhibitor of Plk1
Cas No.:755038-02-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment: [1] | |
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Cell lines |
HeLa-S3 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 μM, 24 hours |
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Applications |
The effect of BI 2536 on the cell-cycle profile of cancer cells grown in vitro was assessed by immunofluorescence microscopy and flow cytometry. BI2536 caused HeLa cells to accumulate with a 4N DNA content, indicative of a cell-cycle block in either G2 phase or mitosis. The mitotic figures observed in BI 2536-treated cultures of HeLa cells displayed abnormal mitotic figures at EC50 values closely matching the induction of a G2/M arrest. |
| Animal experiment: [1] | |
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Animal models |
Immunodeficient nu/nu mice injected with HCT 116 cells |
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Dosage form |
Intravenous injection, 40–50mg/kg, once or twice per week |
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Applications |
The administration of BI 2536 was found to be highly efficacious in diverse xenograft models, such as the HCT 116 colon cancer with complete tumor suppression with the twice per week schedule and a T/C value of 16% with once per week treatment. By using a more rigorous model of larger HCT 116 tumors, in which treatment was delayed until cancer nodules reached a median size of 500 mm3, it was found that five cycles of BI 2536 induced marked tumor regressions, whereas the control mice showed progressive disease. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Steegmaier M, Hoffmann M, Baum A, et al. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Current Biology, 2007, 17(4): 316-322. |
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BI 2536 is a potent, ATP-competitive, well tolerated and highly specific human polo-like kinase 1 (PLK1) inhibitor with IC value of 0.83 nM, which shows 1000-fold selectivity against other kinases [1].
BI 2536 has been demonstrated to suppress cell growth and colony formation, it has been shown to induce mitotic arrest at G2/M phase and apoptosis in human cervical adenocarcinoma cell line HeLa [2].
BI 2536 has shown to have the effect of inhibiting cell proliferation in more than 20 tumor cell lines with half maximal effective concentration (EC50) values ranging from 2–25 nM. In vivo, multiple studies in xenograft models of human carcinoma have shown the anti-tumor activity of BI 2536 when the drug was intravenously administered 1-2 times every week [1].
References:
[1] Schöffski P. Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist. 2009 Jun;14(6):559-70.
[2] Pezuk JA1, Brassesco MS, Oliveira JC, Morales AG, Montaldi AP, Sakamoto-Hojo ET, Scrideli CA, Tone LG. Antiproliferative in vitro effects of BI 2536-mediated PLK1 inhibition on cervical adenocarcinoma cells. Clin Exp Med. 2013 Feb;13(1):75-80.
| 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。
BI 2536 induces gasdermin E-dependent pyroptosis in ovarian cancer
Background: The frequent emergence of drug resistance to chemotherapy is a major obstacle for the treatment of ovarian cancer. There is a need for novel drugs to fulfill this challenge. Pyroptosis-inducing drugs can inhibit tumor growth. However, their roles in ovarian cancer have not been demonstrated. Methods: We tested the effectiveness of a novel drug, BI 2536, which we found in colorectal cancer. Cell proliferation, cell cycle, and drug-induced apoptosis and pyroptosis were tested. In vivo treatments were performed using a cell-derived xenograft model. Results: BI 2536 significantly inhibited the proliferation of ovarian cancer cells and induced cell cycle arrest at the G2/M phases. After BI 2536 treatment, DNA fragmentation and PS exposure on the outside of apoptotic cells were detected. Moreover, the pyroptotic phenotype of ovarian cancer cells along with the release of LDH and HMGB1 were observed, indicating the leakage of cells. Western blot analysis verified that BI 2536 induced GSDME-mediated pyroptosis. Pyroptosis was abolished after additional treatment with Z-DEVD-FMK, a caspase-3 inhibitor. Thus, BI 2536 induced pyroptosis in ovarian cancer through the caspase-3/GSDME pathway. In vivo experiments further demonstrated the antitumoral effect and ability of BI 2536 to accumulate CD8+ T cells in ovarian cancer. Conclusion: In this study, we identified BI 2536 as an effective anti-ovarian cancer drug that inhibits proliferation, arrests the cell cycle, induces apoptosis and pyroptosis, and leads to the accumulation of CD8+ T cells in tumor sites. Drug-induced pyroptosis may have promising prospects for reducing side effects and activating immune responses.
BI-2536 Promotes Neuroblastoma Cell Death via Minichromosome Maintenance Complex Components 2 and 10
DNA replication is initiated with the recognition of the starting point of multiple replication forks by the origin recognition complex and activation of the minichromosome maintenance complex 10 (MCM10). Subsequently, DNA helicase, consisting of the MCM protein subunits MCM2-7, unwinds double-stranded DNA and DNA synthesis begins. In previous studies, replication factors have been used as clinical targets in cancer therapy. The results showed that MCM2 could be a proliferation marker for numerous types of malignant cancer. We analyzed samples obtained from patients with neuroblastoma, revealing that higher levels of MCM2 and MCM10 mRNA were associated with poor survival rate. Furthermore, we combined the results of the perturbation-induced reversal effects on the expression levels of MCM2 and MCM10 and the sensitivity correlation between perturbations and MCM2 and MCM10 from the Cancer Therapeutics Response Portal database. Small molecule BI-2536, a polo-like kinase 1 (PLK-1) inhibitor, is a candidate for the inhibition of MCM2 and MCM10 expression. To test this hypothesis, we treated neuroblastoma cells with BI-2536. The results showed that the drug decreased cell viability and reduced the expression levels of MCM2 and MCM10. Functional analysis further revealed enrichments of gene sets involved in mitochondria, cell cycle, and DNA replication for BI-2536-perturbed transcriptome. We used cellular assays to demonstrate that BI-2536 promoted mitochondria fusion, G2/M arrest, and apoptosis. In summary, our findings provide a new strategy for neuroblastoma therapy with BI-2536.
BI-2536 and BI-6727, dual Polo-like kinase/bromodomain inhibitors, effectively reactivate latent HIV-1
HIV-1 latent reservoirs harbouring silenced but replication-competent proviruses are a major obstacle against viral eradication in infected patients. The "shock and kill" strategy aims to reactivate latent provirus with latency reversing agents (LRAs) in the presence of antiretroviral drugs, necessitating the development of effective and efficient LRAs. We screened a chemical library for potential LRAs and identified two dual Polo-like kinase (PLK)/bromodomain inhibitors, BI-2536 and BI-6727 (volasertib), which are currently undergoing clinical trials against various cancers. BI-2536 and BI-6727 significantly reactivated silenced HIV-1 provirus at both the mRNA and protein level in two latently infected model cell lines (ACH2 and U1). BI-2536 dramatically reactivated transcription of latent HIV-1 provirus in peripheral blood mononuclear cells derived from infected patients. Long terminal repeat activation by the inhibitors was associated with bromodomain rather than PLK inhibition. We also found that BI-2536 synergistically activates the latent provirus in combination with SAHA, a histone deacetylase inhibitor, or the non-tumour-promoting phorbol ester prostratin. Our findings strongly suggest that BI-2536 and BI-6727 are potent LRAs for the "shock and kill" HIV-1 eradication strategy.
BI_2536--targeting the mitotic kinase Polo-like kinase 1 (Plk1)
Human Polo-like kinase 1 (Plk1) is an essential regulator of mitotic progression. Targeted inhibition of this kinase was effective in killing tumor cells in vitro and in vivo. The Plk1 inhibitor BI_2536 was well tolerated and showed antitumor activity in the first clinical trials enrolling patients with advanced solid tumors and refractory or relapsed acute myeloid leukemia.
Connectivity Mapping Identifies BI-2536 as a Potential Drug to Treat Diabetic Kidney Disease
Diabetic kidney disease (DKD) remains the most common cause of kidney failure, and the treatment options are insufficient. Here, we used a connectivity mapping approach to first collect 15 gene expression signatures from 11 DKD-related published independent studies. Then, by querying the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 data set, we identified drugs and other bioactive small molecules that are predicted to reverse these gene signatures in the diabetic kidney. Among the top consensus candidates, we selected a PLK1 inhibitor (BI-2536) for further experimental validation. We found that PLK1 expression was increased in the glomeruli of both human and mouse diabetic kidneys and localized largely in mesangial cells. We also found that BI-2536 inhibited mesangial cell proliferation and extracellular matrix in vitro and ameliorated proteinuria and kidney injury in DKD mice. Further pathway analysis of the genes predicted to be reversed by the PLK1 inhibitor was of members of the TNF-汐/NF-百B, JAK/STAT, and TGF-汕/Smad3 pathways. In vitro, either BI-2536 treatment or knockdown of PLK1 dampened the NF-百B and Smad3 signal transduction and transcriptional activation. Together, these results suggest that the PLK1 inhibitor BI-2536 should be further investigated as a novel therapy for DKD.