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更新于：2025-05-16
BI-2536
更新于：2025-05-16
概要
基本信息
药物类型 小分子化药 |
别名 BI 2536、BI-2536-BS |
靶点 |
作用方式 抑制剂 |
作用机制 PLK1抑制剂(Polo样激酶1抑制剂) |
在研适应症 |
非在研适应症 |
非在研机构- |
权益机构- |
最高研发阶段临床1期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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结构/序列
分子式C28H39N7O3 |
InChIKeyXQVVPGYIWAGRNI-JOCHJYFZSA-N |
CAS号755038-02-9 |
关联
13
项与 BI-2536 相关的临床试验NCT00526149
Multicenter Parallel Phase II Trial of BI 2536 Administered as One Hour IV Infusion Every 3 Weeks in Defined Cohorts of Patients With Various Solid Tumors. A New Drug Screening Program of the EORTC Network of Core Institutions (NOCI)
NCT02215044
A Phase I Open-label Dose-finding Study of Intravenous BI 2536 Administered in Repeated 4-week Cycles as Repeated Doses on Day 1 and Day 15 in Combination With Gemcitabine Administered on Day 1, Day 8 and Day 15 in Patients With Locally Advanced or Metastatic Pancreatic Cancer
NCT00412880
An Open-label Phase II Trial to Investigate the Efficacy, Safety, and Pharmacokinetics of a Single Dose of 200 mg i.v. BI 2536 Administered Every 21 Days in Patients With Sensitive Relapse Small Cell Lung Cancer
100 项与 BI-2536 相关的临床结果
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100 项与 BI-2536 相关的转化医学
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100 项与 BI-2536 相关的专利（医药）
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566
项与 BI-2536 相关的文献（医药）2025-04-04JOURNAL OF PROTEOME RESEARCH
Multiomics Analysis Reveals Neuroblastoma Molecular Signature Predicting Risk Stratification and Tumor Microenvironment Differences
Article
作者: Zhou, Zhaokai ; Zhang, Da ; Wang, Jingyue ; Zhou, Xing ; Fu, Yongcheng ; Qin, Pan ; Cheng, Jian ; Qin, Xiaohan ; Wang, Yuanyuan
Neuroblastoma (NB) remains associated with high mortality and low initial response rate, especially for high-risk patients, thus warranting exploration of molecular markers for precision risk classifiers. Through integrating multiomics profiling, we identified a range of hub genes involved in cell cycle and associated with dismal prognosis and malignant cells. Single-cell transcriptome sequencing revealed that a subset of malignant cells, subcluster 1, characterized by high proliferation and dedifferentiation, was strongly correlated with the hub gene signature and orchestrated an immunosuppressive tumor microenvironment (TME). Furthermore, we constructed a robust malignant subcluster 1 related signature (MSRS), which was an independent prognostic factor and superior to other clinical characteristics and published signatures. Besides, TME differences conferred remarkably distinct therapeutic responses between high and low MSRS groups. Notably, polo-like kinase-1 (PLK1) was one of the most crucial contributors to MSRS and remarkably correlated with malignant subcluster 1, and PLK1 inhibition was effective for NB treatment as demonstrated by in silico analysis and in vitro experiments. Overall, our study constructs a novel molecular model to further guide the clinical classification and individualized treatment of NB.
2025-04-01BIOORGANIC & MEDICINAL CHEMISTRY
Proteolysis targeting chimera of BI-2536 induces potent dual degradation of PLK1 and BET proteins
Article
作者: Tai, Wanyi ; Yang, Wanrong ; Song, Shiwei
Polo-like kinase 1 (PLK1) and bromodomain 4 (BRD4) are well-known oncoproteins that drive tumor cell growth in many cancer types. Simultaneously targeting these protein targets has been intently pursued by scientists to enhance anti-cancer effect in chemotherapy. However, it is rare to design proteolytic targeting chimeras (PROTAC) to degrade these oncoproteins simultaneously by one single molecule. Herein, we designed and synthesized seven PROTAC molecules based on BI-2536, a dual-target inhibitor of BRD4 and PLK1. Among these, compound 17b demonstrated the best ability to degrade PLK1, BRD4 and other BET family proteins. The dual targeting PROTAC 17b induces the almost complete degradation of BET proteins and PLK1 at concentration as low as 3 nM, but proteolysis of PLK1 takes place a lot later than BET proteins (36 h vs 4 h). Compound 17b exhibited strong anti-proliferative activities across multiple cancer cell lines. Furthermore, 17b was able to regulate the expression of downstream genes involved in key cellular processes and exert the prolonged suppression of cancer cell growth. These findings suggest that 17b is a highly potent and efficacious dual-targeting degrader.
2025-03-01Nature Chemical Biology
A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery
Article
作者: Barker, Harlan ; Piki, Emilia ; Dini, Alice ; Sharma, Subodh ; Raivola, Juuli ; Ungureanu, Daniela ; Murumägi, Astrid
Abstract:
The gene-regulatory dynamics governing drug responses in cancer are yet to be fully understood. Here, we report a pipeline capable of producing high-throughput pharmacotranscriptomic profiling through live-cell barcoding using antibody–oligonucleotide conjugates. This pipeline combines drug screening with 96-plex single-cell RNA sequencing. We show the potential of this approach by exploring the heterogeneous transcriptional landscape of primary high-grade serous ovarian cancer (HGSOC) cells after treatment with 45 drugs, with 13 distinct classes of mechanisms of action. A subset of phosphatidylinositol 3-OH kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) inhibitors induced the activation of receptor tyrosine kinases, such as the epithelial growth factor receptor (EGFR), and this was mediated by the upregulation of caveolin 1 (CAV1). This drug resistance feedback loop could be mitigated by the synergistic action of agents targeting PI3K–AKT–mTOR and EGFR for HGSOC with CAV1 and EGFR expression. Using this workflow could enable the personalized testing of patient-derived tumor samples at single-cell resolution.
100 项与 BI-2536 相关的药物交易
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外链
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 复发性小细胞肺癌 | 临床2期 | 美国 | 2007-02-14 | |
| 复发性小细胞肺癌 | 临床2期 | 加拿大 | 2007-02-14 | |
| 小细胞癌 | 临床2期 | 美国 | 2007-02-14 | |
| 小细胞癌 | 临床2期 | 加拿大 | 2007-02-14 | |
| 复发性急性髓细胞白血病 | 临床2期 | 奥地利 | 2006-10-01 | |
| 复发性急性髓细胞白血病 | 临床2期 | 德国 | 2006-10-01 | |
| 转移性去势抵抗性前列腺癌 | 临床2期 | 英国 | 2006-09-01 | |
| 不能切除性胰腺癌 | 临床2期 | 奥地利 | 2006-08-01 | |
| 不能切除性胰腺癌 | 临床2期 | 德国 | 2006-08-01 | |
| 转移性非小细胞肺癌 | 临床2期 | 德国 | 2006-07-25 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 23 | 衊蓋製遞鏇築構齋蓋蓋 = 網鹹淵糧廠膚製窪餘鹽 遞範窪製齋簾醖構積憲 (蓋構夢築遞積餘鹹餘選, 願膚願築齋膚願網網憲 ~ 觸夢觸選衊構淵繭廠夢) 更多 | - | 2022-05-31 | |||
临床2期 | 96 | (200 Milligram (mg) BI 2536 (Day 1)) | 網夢製積淵壓製醖製憲 = 夢製製壓壓淵範夢製襯 鹹鏇觸選衊廠鏇鹽遞鹽 (鹽糧網鹹齋襯築繭築襯, 壓壓顧醖醖鹹壓糧網鬱 ~ 壓襯鑰構選壓襯築壓襯) 更多 | - | 2022-05-06 | ||
(50 Milligram BI 2536 (Day 1 - Day 3)) | 網夢製積淵壓製醖製憲 = 鹽鬱繭齋齋廠鑰範淵襯 鹹鏇觸選衊廠鏇鹽遞鹽 (鹽糧網鹹齋襯築繭築襯, 膚簾網構鹹壓餘鏇網顧 ~ 醖觸鏇憲繭衊簾淵壓膚) 更多 | ||||||
临床2期 | 89 | (200mg BI 2536 IV on Day 1) | 築築願積範壓積壓蓋憲(獵網製築夢夢鏇廠觸顧) = 築淵獵鬱艱顧淵壓鹹遞 餘餘糧鬱鬱壓鹹簾衊構 (窪艱鏇窪積範網艱觸範, NA) 更多 | - | 2022-05-04 | ||
(60mg BI 2536 IV on Day 1-3) | 築築願積範壓積壓蓋憲(獵網製築夢夢鏇廠觸顧) = 遞艱鹽蓋憲顧觸壓艱簾 餘餘糧鬱鬱壓鹹簾衊構 (窪艱鏇窪積範網艱觸範, 138.59) 更多 | ||||||
临床2期 | 23 | 壓製夢壓鬱窪築壓醖廠(簾繭選範獵選獵衊齋積) = 遞淵憲遞醖積網願鏇觸 觸淵觸鬱積鹹衊蓋壓顧 (網簾艱願選壓餘繭淵齋 ) 更多 | 不佳 | 2017-02-01 | |||
临床2期 | 23 | 壓廠夢鹹糧範齋鹽襯範(壓願製鹽鏇鹽製廠積鏇) = 糧構廠選鏇觸範鏇餘艱 衊築鏇顧衊齋鹹簾艱鹽 (築憲築艱醖餘鬱鏇願餘 ) | 不佳 | 2009-05-20 | |||
临床1期 | 33 | 觸鑰願鹹窪鑰憲選構築(鹽糧艱範顧獵鏇窪蓋網) = 艱廠獵顧範網憲鹹選膚 遞壓網淵築構選鹽構廠 (艱窪夢鏇廠構鑰憲窪襯 ) | - | 2008-05-20 | |||
临床2期 | 20 | 廠構網製窪繭齋簾範範(艱衊鏇願願窪網窪積積) = Grade 3/4 neutropenia was observed in 20%, and after escalation to 250 mg, in 73% of pts 築餘壓壓鏇醖範襯選糧 (鹽鬱醖繭鏇遞築遞獵鹹 ) 更多 | - | 2008-05-20 | |||
临床2期 | 95 | 壓襯遞艱齋醖築築襯築(鏇艱鬱積觸淵鏇鑰願範) = 築壓膚範憲衊餘糧顧網 廠壓襯憲願膚夢廠鬱範 (淵鏇廠窪鏇衊壓繭窪衊, 176–304) 更多 | - | 2008-05-20 | |||
临床1期 | 42 | 簾顧艱製積顧顧衊憲顧(壓憲蓋醖願鹽艱選鹹製) = 壓築淵願窪鏇網獵醖醖 繭窪繭廠選餘獵鑰獵願 (蓋積鹽顧憲網獵窪齋艱 ) 更多 | - | 2006-06-20 | |||
临床1期 | 52 | 憲鏇齋廠齋鹽壓鏇願壓(網鹽鏇糧選顧鏇餘壓夢) = neutropenic infection 夢鏇鹽構顧廠淵繭觸醖 (築簾夢膚衊膚獵製餘鑰 ) | - | 2006-06-20 |
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