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.

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

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 / Recruiting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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16

项与 Verubulin 相关的文献（医药）

2023-03-27·Pharmaceuticals (Basel, Switzerland)

Binding Parameters of [¹¹C]MPC-6827, a Microtubule-Imaging PET Radiopharmaceutical in Rodents.

Article

作者: Bhoopal, Bhuvanachandra ; Gollapelli, Krishna Kumar ; Krizan, Ivan ; Craft, Suzanne ; Mintz, Akiva ; Bansode, Avinash H. ; Solingapuram Sai, Kiran Kumar ; Damuka, Naresh ; Miller, Mack

Impairment and/or destabilization of neuronal microtubules (MTs) resulting from hyper-phosphorylation of the tau proteins is implicated in many pathologies, including Alzheimer's disease (AD), Parkinson's disease and other neurol. disorders.Increasing scientific evidence indicates that MT-stabilizing agents protect against the deleterious effects of neurodegeneration in treating AD.To quantify these protective benefits, we developed the first brain-penetrant PET radiopharmaceutical, [11C]MPC-6827, for in vivo quantification of MTs in rodent and nonhuman primate models of AD.Mechanistic insights revealed from recently reported studies confirm the radiopharmaceutical's high selectivity for destabilized MTs.To further translate it to clin. settings, its metabolic stability and pharmacokinetic parameters must be determinedHere, we report in vivo plasma and brain metabolism studies establishing the radiopharmaceutical-binding constants of [11C]MPC-6827.Binding constants were extrapolated from autoradiog. experiments; pretreatment with a nonradioactive MPC-6827 decreased the brain uptake >70%.It exhibited ideal binding characteristics (typical of a CNS radiopharmaceutical) including LogP (2.9), Kd (15.59 nM), and Bmax (11.86 fmol/mg).Most important, [11C]MPC-6827 showed high serum and metabolic stability (>95%) in rat plasma and brain samples.

2022-10-01·Bioorganic & Medicinal Chemistry Letters

Radiosynthesis and evaluation of [11C]AG-488, a dual anti-angiogenetic and anti-tubulin PET ligand

Article

作者: Mintz, Akiva ; Molotkov, Andrei ; Neelamegam, Ramesh ; Dileep Kumar, J S ; Chaly, Thomas ; Carberry, Patrick

Combinations of antiangiogenic and cytotoxic agents show promising results in the treatment of cancer. However, there is a lack of single agent with both antiangiogenic and cytotoxic activities for clinical application. AG-488 aka FLAG-003 is a novel ligand with established antiangiogenetic properties via activation of receptor thymidine kinase (RTK) and anti-tubulin properties in tumor cells. AG-488 is also reported to reduce tumor volume and prolong survival in preclinical animal models of glioblastoma multiforme, breast cancer and is in clinical stage. Higher expression of RTKs and tubulins is reported in various cancers. This study reveals the development of [¹¹C]AG-488, a high affinity dual target inhibitor binding to RTK and anti-tubulin activities. We rationale that antiangiogenic RTK and anti-tubulin activity of [¹¹C]AG-488 may enhance the tumor to tissue ratio, assisting in cancer drug development. [¹¹C]AG-488 was synthesized in 35 ± 5 % radiochemical yield by radiomethylating the corresponding phenolate using [¹¹C]CH₃I. MicroPET studies in mice indicated blood-brain barrier penetration of [¹¹C]AG-488 and retention in the brain. However, blocking studies with antitubulin and RTK agent HD-800 and microtubule depolymerizing agent MPC-6827 show increased binding of [¹¹C]AG-488 in brain. The pattern of tracer binding in blocking conditions is similar to the baseline conditions. The higher binding may be due to the increased plasma uptake of radiotracer or the formation of more free tubulins due to microtubule dynamic instability during the blocking conditions.

2019-03-01·Bioorganic Chemistry2区 · 化学

Discovery of novel quinazolines as potential anti-tubulin agents occupying three zones of colchicine domain

2区 · 化学

Article

作者: Xu, Jinyi ; Shuai, Wen ; Liu, Jie ; Zhu, Zheying ; Yao, Hong ; Xu, Shengtao ; Xu, Feijie ; Cheng, Keguang ; Li, Wenlong ; Yin, Ying

A series of novel quinazolines as tubulin inhibitors occupying three zones of colchicine domain have been designed and synthesized inspired by the recently disclosed crystal structure of verubulin analogue 6 with tubulin. Among the newly synthesized compounds, 19c showed noteworthy potency against K562, HepG2, KB, HCT-8 and MDB-MB-231 cancer cells. In vitro microtubule polymerization assays identified 19c as a potent tubulin assembly inhibitor, the binding mode of which with tubulin was confirmed by molecular modeling studies to occupy three zones of tubulin domain. Furthermore, 19c disrupted the intracellular microtubule network, caused G2/M phase arrest, induced cell apoptosis and depolarized mitochondria of K562 cells. 19c also reduced the cell migration and disrupted the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Importantly, 19c significantly and dose dependently inhibited tumor growth in H22 liver cancer xenograft mouse model. All these results suggested that 19c deserves further research as a novel and potential anti-tubulin agent for the treatment of cancers.

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
脑癌	临床2期	-	Immune Pharmaceuticals, Inc.	-
神经系统变性病	临床1期	美国	Myrexis, Inc.	2020-09-25
结直肠癌	临床1期	美国	Immune Pharmaceuticals, Inc.	-
脑转移瘤	药物发现	美国	Immune Pharmaceuticals, Inc.	2016-01-03
黑色素瘤	药物发现	美国	Immune Pharmaceuticals, Inc.	2015-12-29
胶质母细胞瘤	药物发现	美国	Immune Pharmaceuticals, Inc.	2015-12-19
多形性胶质母细胞瘤	药物发现	美国	Myrexis, Inc.	2009-04-01
复发性胶质母细胞瘤	药物发现	美国	Myrexis, Inc.	2009-04-01
难治恶性实体肿瘤	药物发现	美国	Myrexis, Inc.	2005-03-01

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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


ASCO2011	临床2期	复发性胶质母细胞瘤	31	Verubulin	醖鹹顧鬱壓壓範觸糧憲(網選積憲積願構築壓選) = 簾鑰糧淵窪繭淵築積艱鏇鹹夢觸衊願衊艱製獵 (顧餘鹽夢遞觸鏇壓遞網, 3% ~ 25%) 更多	积极	2011-05-20
ASCO2010	N/A	转移性黑色素瘤	22	MPC-6827	(鹽範餘艱醖選窪選餘艱) = 遞選鏇壓鹽艱蓋醖窪夢壓鹹蓋積網構鬱淵壓鑰 (鏇鏇遞鑰顧膚製廠選衊, [1.7 ~ 5.5])	-	2010-05-20
ASCO2010	N/A	复发性胶质母细胞瘤	19	MPC-6827	(淵觸網願膚夢糧願鹹築) = 獵窪選艱蓋膚鬱簾獵憲築繭膚觸遞齋鏇構顧願 (選淵網窪餘鑰壓鬱鬱壓, [1.3 ~ 7.1]) 更多	-	2010-05-20
AACR2009	临床1期	实体瘤	48	Azixa	(鑰糧蓋壓選膚憲範鏇夢) = 艱製夢糧襯壓選鏇範艱餘淵遞遞膚顧糧鬱膚積 (糧衊鹹膚簾範膚壓衊積 )	-	2009-05-01
ASCO2007	临床1期	HR阳性/HER2低表达实体瘤 \| 脑转移瘤	-	MPC-6827	(鹽積糧構醖選齋鹽鹹糧) = 鹽餘衊膚鹽築齋壓鹹齋廠獵廠遞鑰製繭鬱範願 (蓋鏇壓範夢繭壓蓋壓製 )	-	2007-06-20