Mivebresib(Mivebresib) - 药物靶点：BRD4_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Mivebresib (USAN/INN)、ABB075、ABBV-075

靶点

BRD4

作用方式

抑制剂

作用机制

BRD4抑制剂(溴结构域蛋白-4抑制剂)、表观遗传学药物

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病+ [4]

在研适应症-

非在研适应症

急性髓性白血病晚期癌症乳腺癌+ [7]

原研机构

AbbVie, Inc.

在研机构-

非在研机构

AbbVie, Inc.

权益机构-

最高研发阶段终止临床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C22H19F2N3O4S

InChIKeyRDONXGFGWSSFMY-UHFFFAOYSA-N

CAS号1445993-26-9

关联

2

项与 Mivebresib 相关的临床试验

NCT04480086

/ Terminated临床1期

A Phase 1b Study of Mivebresib Alone or in Combination With Ruxolitinib or Navitoclax in Subjects With Myelofibrosis

Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The purpose of this study is to see how safe and tolerable mivebresib is, when given alone, and in combination with navitoclax or ruxolitinib, for adult participants with MF.
Mivebresib is an investigational drug being developed for the treatment of MF. The study has 4 segments - A, B, C, and D. In Segment A, the safe dosing regimen of mivebresib is identified, and then given alone as monotherapy. In Segment B, C, and D, combination therapies of mivebresib with either ruxolitinib or navitoclax are given. Adult participants with a diagnosis of MF will be enrolled. Around 130 participants will be enrolled in 60 sites worldwide.
In Segment A, participants will receive different doses and schedules of oral mivebresib tablet to identify a safe dosing regimen. Additional participants will be enrolled at the identified monotherapy dosing regimen. In Segment B, participants will receive oral ruxolitinib and mivebresib will be given as "add-on" therapy. In Segment C, participants will receive mivebresib and oral navitoclax. In Segment D, participants will receive mivebresib and ruxolitinib. Participants will receive treatment until disease progression or the participants are not able to tolerate the study drugs.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.

开始日期2021-03-17

申办/合作机构

AbbVie, Inc.

NCT02391480

/ Completed临床1期

A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABBV-075 in Subjects With Advanced Cancer

This is a Phase 1, first-in-human, dose escalation study in participants with advanced solid tumors to determine the pharmacokinetics, maximum tolerated dose and the recommended Phase 2 dose of ABBV-075 at different monotherapy dosing schedules. In addition the study will evaluate the safety. tolerability and the pharmacokinetics of ABBV-075 monotherapy or combination therapy in disease specific expansion cohorts.

开始日期2015-04-14

申办/合作机构

AbbVie, Inc.

100 项与 Mivebresib 相关的临床结果

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100 项与 Mivebresib 相关的转化医学

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100 项与 Mivebresib 相关的专利（医药）

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65

项与 Mivebresib 相关的文献（医药）

2025-12-01·DRUG DISCOVERY TODAY

Inhibition of bromodomain and extra-terminal motif (BET) proteins in pediatric sarcoma: A systematic review of in vitro and in vivo studies

Review

作者: Lambona, Chiara ; Rota, Rossella ; Marchese, Cinzia ; Locatelli, Franco ; Zwergel, Clemens ; Cassandri, Matteo ; Macrì, Elisa ; Pomella, Silvia ; Barillari, Giovanni ; Ferraro, Erika

BET inhibitors (BETi), especially those targeting BRD4, show promising preclinical activity against pediatric sarcomas by disrupting oncogenic transcription. This systematic review of 26 studies highlights the anti-proliferative and pro-apoptotic effects of BETi across five pediatric sarcoma types. In vivo data show a decrease in tumor growth, with better results when combined with other therapies. This systematic review revealed that, whereas early investigations mostly rely on pan-BETi, recent studies focus on newer and more specific agents. Accordingly, we reported that ABBV-744 and RVX-208, which selectively target the BD2 domain, and GNE-987, a specific BRD4 degrader, are the most promising inhibitors. However, ABBV-075, a pan-BETi, also exhibits high efficacy, being effective at low doses. Nevertheless, translating these experimental findings into clinical practice remains difficult because of resistance, toxicity, and inconsistent responses. Future approaches include using biomarkers for patient selection, developing isoform-specific BETi, and designing rational combination therapies to enhance treatment for these aggressive pediatric cancers.

2025-12-01·NEOPLASIA

Identification of BET inhibitors (BETi) against solitary fibrous tumor (SFT) through high-throughput screening (HTS)

Article

作者: Li, Yi ; Wei, Shuguang ; Hayenga, Heather N ; Marti, Jesus L ; Posner, Bruce A ; Mondaza-Hernandez, Jose L ; Moura, David S ; Gomez-Puertas, Paulino ; Nguyen, John T ; Bleris, Leonidas ; Martin-Broto, Javier ; Meyer, Clark A

Cancers, especially fusion oncoprotein (FO)-driven hematological cancers and sarcomas, often develop from a low number of key mutations. Solitary Fibrous Tumor (SFT) is a rare mesenchymal tumor driven by the NAB2-STAT6 oncofusion gene. Currently, the treatment options for SFT remain limited, with anti-angiogenic drugs providing only partial responses with an average survival of two years. We constructed SFT cell models harboring specific NAB2-STAT6 fusion transcripts using the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology, and we used these cells as models of SFT. High-throughput drug screens demonstrated that the BET inhibitor Mivebresib can differentially reduce proliferation in SFT cell models. Subsequently, BET inhibitors Mivebresib and BMS-986158 efficiently reduced tumor growth in an SFT patient-derived xenograft (PDX) animal model. Furthermore, our data showed that NAB2-STAT6 fusions may lead to high levels of DNA damage in SFTs. Consequently, combining BET inhibitors with PARP (Poly (ADP-ribose) polymerase) inhibitors or with ATR inhibitors significantly enhanced anti-proliferative effects in SFT cells. Taken together, this study establishes BET inhibitors Mivebresib and BMS-986158 as promising anti-SFT agents.

2025-06-01·Nature Chemical Biology

Catalytic-independent functions of the Integrator–PP2A complex (INTAC) confer sensitivity to BET inhibition

Article

作者: Chen, Shuo ; Meng, Xiao-Ming ; Shen, Hongjie ; Wang, Zhenning ; Xu, Congling ; Liu, Jiaxian ; Cheng, Jingdong ; Hong, Lei ; Shang, Xue-Ying ; Song, Aixia ; Jiang, Wei ; Yang, Huijuan ; Jiang, Hai ; Ma, Jingchuan ; Zhang, Qi ; Lan, Fei ; Zhang, Peng ; Mao, Run-Yuan ; Chen, Jiwei ; Chen, Fei Xavier ; Tao, Bolin ; Zheng, Hai ; Xu, Wei ; Fan, Pengyu

Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics. This process bypasses a requirement for the catalytic activities of INTAC and instead leverages direct engagement of the auxiliary module with the RACK7/ZMYND8-KDM5C complex to remove histone H3K4 methylation. Targeted degradation of the COMPASS subunit WDR5 to attenuate H3K4 methylation restores sensitivity to BET inhibitors, highlighting how simultaneously targeting coordinated chromatin and transcription regulators can circumvent drug-resistant tumors.

1

项与 Mivebresib 相关的新闻（医药）

2025-04-25

·药学进展

学科前沿 | 清华大学生命学院郗乔然研究组联合临床团队揭示了弥漫内生型脑桥胶质瘤潜在的表观遗传治疗靶点

“点击蓝字关注我们清华大学生命学院郗乔然研究组联合临床团队揭示了弥漫内生型脑桥胶质瘤潜在的表观遗传治疗靶点 PPS 弥漫内生型脑桥胶质瘤（Diffuse Intrinsic Pontine Glioma，DIPG）是一种高度致命的儿童脑瘤，被称为“儿童杀手”或“死亡恶魔”。该病主要发生于6至7岁儿童脑干的脑桥区域，呈弥漫性生长，属于儿童高级别胶质瘤（pHGG）中最具恶性的一种。由于肿瘤位于“手术禁区”，手术切除几乎不可能。尽管已有超过300项药物治疗的临床试验，但目前仅有放疗可暂时缓解症状，生存期延长有限，五年生存率甚至低于1%。因此，攻克DIPG成为全球神经科学与肿瘤学界的重大难题。2025年4月17日，清华大学生命科学学院郗乔然课题组与首都医科大学附属天坛医院张力伟课题组合作，在《自然·通讯》(Nature Communications) 杂志发表题为 “一种由癌组蛋白驱动的 H3.3K27M/CREB5/ID1 轴维持弥漫内生型脑桥胶质瘤的干性和恶性特征”（An oncohistone-driven H3.3K27M/CREB5/ID1 axis maintains the stemness and malignancy of diffuse intrinsic pontine glioma）的研究论文。该研究系统性阐释了癌组蛋白H3.3K27M通过重塑表观遗传景观激活转录因子CREB5，进而调控ID1表达，从而维持DIPG的干性与恶性，为临床治疗提供了潜在的表观遗传靶点。这项工作是继两个研究团队此前在 Nature Cancer上报道BMP信号通路在不同亚型的DIPG中呈现不同活性后（H3.1K27M亚型BMP信号增强，H3.3K27M亚型BMP信号抑制），进一步深入解析了BMP下游关键靶基因ID1的激活机制。研究表明，尽管在H3.3K27M亚型中BMP信号被抑制，ID1依然高度表达，其表达并非由BMP信号直接驱动，而是由CREB5转录因子通过超级增强子直接激活。这一发现打破了传统“通路—靶基因”线性调控的理解，揭示了癌组蛋白通过CREB5-ID1轴重塑DIPG干性表型的新机制。进一步研究显示，CREB5在正常小鼠脑桥中表达极低，受到HOXA基因簇介导的H3K27me3表观遗传沉默，而在H3.3K27M突变的DIPG细胞中，PRC2功能变化导致H3K27me3水平下降，CREB5因而异常激活。CREB5随后与SWI/SNF复合物核心亚基BRG1协同，激活ID1等下游干性因子，维持肿瘤的干性与增殖能力。体内外实验均表明，敲低CREB5显著抑制DIPG细胞的干性特征与成瘤能力，并延长免疫缺陷小鼠生存期。药物筛选层面，研究团队鉴定出小分子抑制剂ABBV-075可抑制CREB5超级增强子活性，降低CREB5表达、抑制肿瘤生长。联合使用ABBV-075与BRG1抑制剂则产生更显著的协同效果，为表观遗传靶向治疗DIPG提供了新方向。此研究不仅进一步揭示了癌组蛋白在DIPG中重塑转录网络的分子机制，还延续并深化了团队此前关于BMP通路功能差异性的研究成果，为儿童DIPG基础机制研究和临床转化奠定了坚实基础，带来新的治疗希望。清华大学生命学院郗乔然副教授、首都医科大学附属天坛医院张力伟教授为该论文共同通讯作者。清华大学生命学院2019级博士生周威与天坛医院医师徐骋为共同第一作者。生命学院2022级本科生杨双瑞与2019级本科生李浩成参与了实验工作。上海交通大学唐玉杰教授提供了部分DIPG细胞系。生命学院米达副教授团队成员李晓寒和乔慧敏提供了发育小鼠脑片，天坛医院泮长存、蒋壮与谢璐阳提供了临床样本与信息支持。原文链接：https://doi.org/10.1038/s41467-025-58795-2文章来源：清华大学生命学院美编排版：史鑫宇文章审核：周碧远史鑫宇罗琪【免责声明】以上内容来源于互联网，不代表本平台立场或观点；如有侵犯作者著作权，请及时与我们联系（Tel：025-83271227，或直接在微信平台留言），我们将及时更正或删除。《药学进展》杂志由国家教育部主管、中国药科大学和中国药学会共同主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.216，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐聚焦“兴药为民·2023生物医药创新融合发展大会”“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟

临床1期临床研究

100 项与 Mivebresib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11479	-	-	-

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
原发性血小板增多症后骨髓纤维化	临床1期	美国	AbbVie, Inc.	2021-03-17
原发性血小板增多症后骨髓纤维化	临床1期	南非	AbbVie, Inc.	2021-03-17
原发性血小板增多症后骨髓纤维化	临床1期	韩国	AbbVie, Inc.	2021-03-17
真性红细胞增多症后骨髓纤维化	临床1期	美国	AbbVie, Inc.	2021-03-17
真性红细胞增多症后骨髓纤维化	临床1期	南非	AbbVie, Inc.	2021-03-17
真性红细胞增多症后骨髓纤维化	临床1期	韩国	AbbVie, Inc.	2021-03-17
原发性骨髓纤维化	临床1期	美国	AbbVie, Inc.	2021-03-17
原发性骨髓纤维化	临床1期	南非	AbbVie, Inc.	2021-03-17
原发性骨髓纤维化	临床1期	韩国	AbbVie, Inc.	2021-03-17
急性髓性白血病	临床1期	美国	AbbVie, Inc.	2015-04-14

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02391480 (Pubmed \| Cancer) 人工标引	临床1期	急性髓性白血病	44	mivebresib	觸鹹遞簾憲齋鬱鹹鏇膚(糧餘製膚齋願鬱選繭觸) = 鬱壓鏇築蓋鏇壓鹹鹽構鹹衊壓築糧繭製憲憲壓 (鹹廠憲鏇鏇網淵襯積鏇 ) 更多	积极	2021-08-15
NCT02391480 (Pubmed \| Cancer) 人工标引	临床1期	急性髓性白血病	44	venetoclax+mivebresib	觸鹹遞簾憲齋鬱鹹鏇膚(糧餘製膚齋願鬱選繭觸) = 膚醖壓夢憲壓選鹹蓋遞鹹衊壓築糧繭製憲憲壓 (鹹廠憲鏇鏇網淵襯積鏇 ) 更多	积极	2021-08-15
NCT02391480 (Pubmed \| Clin Cancer Res) 人工标引	临床2期	实体瘤	84	Mivebresib (14% uveal melanoma; 11% colorectal; 11% breast; 8% pancreatic; 7% head/neck; 49% others)	窪網廠壓壓壓構餘醖繭(願廠窪襯醖淵獵餘鏇簾) = 願蓋繭淵蓋餘蓋簾顧膚淵鹹鏇築鬱齋簾選觸襯 (憲衊願選鬱製獵築觸鏇, 1.8 ~ 1.9) 更多	积极	2019-11-01
NCT02391480 (Pubmed \| Clin Cancer Res) 人工标引	临床2期	实体瘤	84	Mivebresib (prostate cancer)	-	积极	2019-11-01
NCT02391480 (EHA2019)	临床1期	复发性急性髓细胞白血病	41	Mivebresib monotherapy	獵齋壓願積構鑰築選壓(鹽願鹹醖壓範築積襯製) = 鏇糧鹹膚膚鬱簾遞顧餘願艱鹹遞鬱簾築簾艱衊 (齋餘鹽鹽築構範齋襯艱 ) 更多	-	2019-06-14
NCT02391480 (ASCO2019)	临床1期	复发性急性髓细胞白血病	41	Mivebresib monotherapy	襯壓築糧簾壓鏇淵憲窪(齋網鬱積觸餘齋網膚醖) = 遞繭積餘襯壓觸餘選齋鹽簾壓糧齋窪餘餘憲積 (築衊窪蓋鹹齋餘艱鬱艱 ) 更多	积极	2019-05-26
NCT02391480 (ASCO2019)	临床1期	复发性急性髓细胞白血病	41	Mivebresib combined with venetoclax	夢積鹹壓遞範壓製壓顧(網遞膚築繭糧簾蓋觸淵) = 糧鹹醖齋鏇選廠餘簾簾觸遞鹹繭淵選範鏇衊網 (鹹膚夢繭衊醖網願憲蓋 ) 更多	积极	2019-05-26
NCT02391480 (ASCO2019)	临床1期	葡萄膜黑色素瘤	10	Mivebresib (ABBV-075)	願遞糧壓憲憲簾簾襯憲(壓製艱獵蓋夢糧製齋網) = 9 patients experienced a treatment-emergent adverse event (TEAE), most commonly (≥40% patient incidence), dysgeusia (60%), thrombocytopenia and nausea (40%, each) 網遞製獵選網顧願鹹齋 (膚構廠糧艱鹽範鹹製窪 )	-	2019-05-26
NCT02391480 (M14-546, ASCO2018)	临床1期	实体瘤	72	ABBV-075	構願鏇鏇淵顧鏇遞範願(簾觸製網膚築鏇醖廠築) = Dose-limiting toxicities were aspartate aminotransferase elevation 鑰壓範繭餘獵鹹糧築遞 (憲製窪築築獵艱餘艱選 ) 更多	-	2018-06-01
NCT02391480 (M14-546, ASCO2018)	临床1期	葡萄膜黑色素瘤	10	ABBV-075	鬱壓餘簾鏇遞醖製廠鹽(築願範夢鏇鹹獵鏇蓋夢) = 50% 範網餘壓網鬱糧艱繭鬱 (淵蓋糧製鏇蓋齋窪餘鏇 ) 更多	-	2018-06-01
NCT02391480 (ASCO2018)	临床1期	实体瘤	72	ABBV-075	顧膚憲築艱艱艱獵壓積(願淵鬱醖鹽鬱衊窪齋範) = 15.3% vs none 鏇淵鏇壓觸夢願鬱憲淵 (範鹽鏇鏇廠膚製膚廠廠 ) 更多	积极	2018-06-01
NCT02391480 (ASCO2018)	临床1期	复发性急性髓细胞白血病	19	ABBV-075 monotherapy	築範廠選選網繭膚蓋鏇(壓艱鹹遞構顧簾膚艱顧) = 11 衊鑰壓遞壓壓醖觸淵齋 (網築衊築遞蓋願淵衊繭 ) 更多	积极	2018-06-01