Verubulin(Verubulin) - 药物靶点：Tubulin_在研适应症：脑癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Azixa、Veribulin、Verubulin (USAN/INN)

+ [6]

靶点

Tubulin

作用方式

抑制剂

作用机制

微管蛋白抑制剂

治疗领域

肿瘤神经系统疾病

在研适应症

脑癌

非在研适应症

脑转移瘤结直肠癌胶质母细胞瘤+ [5]

原研机构

Immune Pharmaceuticals, Inc.

在研机构

Immune Pharmaceuticals, Inc.

非在研机构

Myrexis, Inc.

权益机构

Immune Pharmaceuticals, Inc.

Myrexis, Inc.

最高研发阶段临床2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C17H17N3O

InChIKeySNHCRNMVYDHVDT-UHFFFAOYSA-N

CAS号827031-83-4

关联

5

项与 Verubulin 相关的临床试验

NCT04575727

/ Completed早期临床1期IIT

Exploratory Evaluation of [11C]MPC6827 Pharmacokinetics With Positron Emission Tomography (PET)

This is a phase 0 study that will enable an assessment of biodistribution and estimation of absorbed dose in humans based on data collected from five healthy volunteers, which is typically the minimum number required by the FDA for first-in-human studies to assess dosimetry of a new tracer. The evaluation of the brain imaging of thirty additional subjects in the 2nd part of the study will lead to a descriptive assessment of the targeting and pharmacokinetics of MPC6827 in the brain and between normal and diseased brain.

开始日期2021-01-08

申办/合作机构

Columbia University

NCT01285414

/ Completed临床2期

A Phase 2 Study of Verubulin With Radiation Therapy and Temozolomide in Subjects Newly Diagnosed With Glioblastoma Multiforme

This, international, multi-center, Phase 2 study of verubulin will be conducted in patients with newly diagnosed Glioblastoma Multiforme (GBM). The study will be conducted in two parts. Part A is an open-label dose finding study that will determine the safety and tolerability of verubulin in combination with standard treatment. Part B is a randomized open-label study that will investigate progression-free survival and overall survival of patients receiving verubulin, at the dose determined in Part A, in combination with standard treatment versus standard treatment alone.

开始日期2010-12-01

申办/合作机构

Myrexis, Inc.

NCT00892931

/ Completed临床2期

Phase 2 Study of Azixa (MPC-6827) for the Treatment of Patients With Recurrent Glioblastoma Multiforme

The purpose of this study is to determine the safety and effectiveness of Azixa in patients with recurrent glioblastoma multiforme

开始日期2009-04-01

申办/合作机构

Myrexis, Inc.

100 项与 Verubulin 相关的临床结果

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100 项与 Verubulin 相关的转化医学

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100 项与 Verubulin 相关的专利（医药）

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48

项与 Verubulin 相关的文献（医药）

2024-12-16·Chemical Research in Toxicology

Quantitative Structure–Activity Relationship Models to Predict Cardiac Adverse Effects

Article

作者: Stavitskaya, Lidiya ; Racz, Rebecca ; Volarath, Patra ; Mou, Zhongyu ; Girireddy, Mounika ; Chakravarti, Suman ; Cross, Kevin P.

Drug-induced cardiotoxicity represents one of the most common causes of attrition of drug candidates in preclinical and clinical development. For this reason, the evaluation of cardiac toxicity is essential during drug development and regulatory review. In the present study, drug-induced postmarket adverse event combinations from the FDA Adverse Event Reporting System were extracted for 2002 drugs using 243 cardiac toxicity-related preferred terms (PTs). These PTs were combined into 12 groups based on their clinical relevance to serve as training sets. The optimal classification scheme was determined using a combination of data sources that included drug labeling information, published literature, clinical study data, and postmarket surveillance data. Two commercial QSAR platforms were used to construct 12 models, including general cardiac toxicity, cardiac ischemia, heart failure, cardiac valve disease, myocardial disease, pericardial disease, structural heart disease, cardiac arrhythmia, Torsades de Pointes, long QT syndrome, atrial fibrillation and ventricular arrhythmia, and cardiac arrest. The cross-validated performance for the new models reached a sensitivity of up to 80% and negative predictivity of up to 80%. These new models covering a wide range of cardiac endpoints will provide fast, reliable, and comprehensive predictions of potential cardiotoxic compounds in drug discovery and regulatory safety assessment.

2024-11-01·European Journal of Medicinal Chemistry

Discovery of novel thiophene[3,2-d]pyrimidine-based tubulin inhibitors with enhanced antitumor efficacy for combined use with anti-pd-l1 immunotherapy in melanoma

Article

作者: Wang, Yuxi ; Chen, Jianjun ; Peng, Xiaopeng ; Zhao, Huiting ; Li, Ling ; Liu, Jin ; Wu, Chengyong ; Xu, Chenglong

Herein, we designed and synthesized a series of novel 2-methylthieno [3,2-d]pyrimidine analogues as tubulin inhibitors with antiproliferative activities at low nanomolar levels. Among them, compound DPP-21 displayed the most potent anti-proliferative activity against six cancer cell lines with an average IC₅₀ of ∼6.23 nM, better than that of colchicine (IC₅₀ = 9.26 nM). DPP-21 exerted its anti-cancer activity by suppressing the polymerization of tubulin with an IC₅₀ of 2.4 μM. Furthermore, the crystal structure of DPP-21 in complex with tubulin was solved by X-ray crystallography to 2.94 Å resolution, confirming the direct binding of DPP-21 to the colchicine site. Moreover, DPP-21 arrested the cell cycle in the G2/M phase of mitosis, subsequently inducing tumor cell apoptosis. Additionally, DPP-21 was able to effectively inhibit the migration of cancer cells. Besides, DPP-21 exhibited significant in vivo anti-tumor efficacy in a B16-F10 melanoma tumor model with a TGI of 63.3 % (7 mg/kg) by intraperitoneal (i.p.) injection. Notably, the combination of DPP-21 with NP-19 (a PD-L1-targeting small molecule inhibitor reported by our group before) demonstrated enhanced anti-cancer efficacy in vivo. These results suggest that DPP-21 is a promising lead compound deserving further investigation as a potential anti-cancer agent.

2024-05-01·Journal of Cellular and Molecular Medicine

Prognostic and immunotherapeutic implications of bilirubin metabolism‐associated genes in lung adenocarcinoma

Article

作者: Li, Zeyao ; Ling, Xiean ; Huang, Tonghai ; Ren, Kangqi ; Chen, Lin

AbstractLung adenocarcinoma (LUAD) is a major subtype of non‐small‐cell lung cancer and accompanies high mortality rates. While the role of bilirubin metabolism in cancer is recognized, its specific impact on LUAD and patient response to immunotherapy needs to be elucidated. This study aimed to develop a prognostic signature of bilirubin metabolism‐associated genes (BMAGs) to predict outcomes and efficacy of immunotherapy in LUAD. We analysed gene expression data from The Cancer Genome Atlas (TCGA) to identify survival‐related BMAGs and construct a prognostic model in LUAD. The prognostic efficacy of our model was corroborated by employing TCGA‐LUAD and five Gene Expression Omnibus datasets, effectively stratifying patients into risk‐defined cohorts with marked disparities in survival. The BMAG signature was indeed an independent prognostic determinant, outperforming established clinical parameters. The low‐risk group exhibited a more favourable response to immunotherapy, highlighted by increased immune checkpoint expression and immune cell infiltration. Further, somatic mutation profiling differentiated the molecular landscapes of the risk categories. Our screening further identified potential drug candidates preferentially targeting the high‐risk group. Our analysis of critical BMAGs showed the tumour‐suppressive role of FBP1, highlighting its suppression in LUAD and its inhibitory effects on tumour proliferation, migration and invasion, in addition to its involvement in cell cycle and apoptosis regulation. These findings introduce a potent BMAG‐based prognostic indicator and offer valuable insights for prognostication and tailored immunotherapy in LUAD.

100 项与 Verubulin 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10029	-	-	DB05585

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
神经退行性疾病	临床2期	美国	Myrexis, Inc.	2020-09-25
脑转移瘤	临床2期	美国	Immune Pharmaceuticals, Inc.	2016-01-03
黑色素瘤	临床2期	美国	Immune Pharmaceuticals, Inc.	2015-12-29
胶质母细胞瘤	临床2期	美国	Immune Pharmaceuticals, Inc.	2015-12-19
多形性胶质母细胞瘤	临床2期	美国	Myrexis, Inc.	2009-04-01
复发性胶质母细胞瘤	临床2期	美国	Myrexis, Inc.	2009-04-01
难治恶性实体肿瘤	临床2期	美国	Myrexis, Inc.	2005-03-01
脑癌	临床2期	-	Immune Pharmaceuticals, Inc.	-
结直肠癌	临床2期	美国	Immune Pharmaceuticals, Inc.	-

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO2011	临床2期	复发性胶质母细胞瘤	31	Verubulin	醖壓遞蓋鹽憲壓齋選網(壓蓋糧艱膚願糧衊鏇鏇) = 襯衊築鏇鑰顧鑰簾壓齋鑰製觸憲衊餘鑰製鑰壓 (鹽範夢蓋網夢襯憲夢選, 3% ~ 25%) 更多	积极	2011-05-20
ASCO2010	N/A	复发性胶质母细胞瘤	19	MPC-6827	(憲鹹鹽餘顧選選選鏇築) = 積襯選遞遞觸鹹廠膚餘鏇構網壓遞鑰襯獵襯窪 (鑰構齋襯壓淵襯願鑰獵, [1.3 ~ 7.1]) 更多	-	2010-05-20
ASCO2010	N/A	转移性黑色素瘤	22	MPC-6827	(蓋膚鏇鬱醖廠鑰網鹹繭) = 鏇鬱選遞構觸鬱鬱鏇壓繭糧顧獵鹽鹽築壓遞積 (簾衊餘簾襯簾鏇齋淵繭, [1.7 ~ 5.5])	-	2010-05-20
AACR2009	临床1期	实体瘤	48	Azixa	(醖顧選鏇築構壓蓋壓壓) = 顧鑰壓鏇醖齋糧繭糧窪襯糧觸餘齋糧範齋網鬱 (鹹夢襯蓋齋遞觸鏇範憲 )	-	2009-05-01
ASCO2007	临床1期	HR阳性/HER2低表达实体瘤 \| 脑转移瘤	-	MPC-6827	(餘鬱齋鹽憲獵積壓築顧) = 選醖蓋簾製醖壓醖蓋鬱築壓艱願鬱願鬱積壓餘 (積衊憲夢淵餘鏇網製壓 )	-	2007-06-20