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、微管蛋白聚合抑制剂

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-

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）

2023-10-21·Pharmaceuticals (Basel, Switzerland)

Verubulin (Azixa) Analogues with Increased Saturation: Synthesis, SAR and Encapsulation in Biocompatible Nanocontainers Based on Ca²⁺ or Mg²⁺ Cross-Linked Alginate.

Article

作者: Leschukov, Denis N ; Zefirov, Nikolay A ; Hrytseniuk, Yanislav S ; Gracheva, Yulia A ; Spiridonov, Vasily V ; Lukmanova, Alina R ; Grishin, Yuri K ; Shevtsova, Elena F ; Averina, Elena B ; Nguyen, Minh T ; Zefirova, Olga N ; Vasilyeva, Lilja A ; Shevtsov, Pavel N ; Spirkova, Elena A ; Markova, Alina A ; Yaroslavov, Alexander A ; Shtil, Alexander A ; Skvortsov, Dmitry A ; Sedenkova, Kseniya N ; Milaeva, Elena R

Tubulin-targeting agents attract undiminished attention as promising compounds for the design of anti-cancer drugs. Verubulin is a potent tubulin polymerization inhibitor, binding to colchicine-binding sites. In the present work, a series of verubulin analogues containing a cyclohexane or cycloheptane ring 1,2-annulated with pyrimidine moiety and various substituents in positions 2 and 4 of pyrimidine were obtained and their cytotoxicity towards cancer and non-cancerous cell lines was estimated. The investigated compounds revealed activity against various cancer cell lines with IC₅₀ down to 1-4 nM. According to fluorescent microscopy data, compounds that showed cytotoxicity in the MTT test disrupt the normal cytoskeleton of the cell in a pattern similar to that for combretastatin A-4. The hit compound (N-(4-methoxyphenyl)-N,2-dimethyl-5,6,7,8-tetrahydroquinazolin-4-amine) was encapsulated in biocompatible nanocontainers based on Ca²⁺ or Mg²⁺ cross-linked alginate and it was demonstrated that its cytotoxic activity was preserved after encapsulation.

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 ; Solingapuram Sai, Kiran Kumar ; Bansode, Avinash H. ; 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: Carberry, Patrick ; Chaly, Thomas ; Neelamegam, Ramesh ; Mintz, Akiva ; Molotkov, Andrei ; Dileep Kumar, J S

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.

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
神经系统变性病	临床3期	美国	Myrexis, Inc.	2020-09-25
结直肠癌	临床3期	美国	Immune Pharmaceuticals, Inc.	-
脑癌	临床2期	-	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

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	衊蓋積憲憲繭顧餘積淵(遞夢積窪範糧廠醖鹹憲) = 獵廠膚範糧鬱選觸壓醖願獵觸襯獵網鹹鏇遞顧 (蓋壓鑰觸鏇夢觸獵觸積, 3%, 25%) 更多	积极	2011-05-20
ASCO2010	N/A	复发性胶质母细胞瘤	19	MPC-6827	(築簾壓醖網網糧顧構鑰) = 遞製艱膚積齋觸淵壓繭簾蓋廠製餘鬱鬱壓衊願 (網餘遞鹽窪構齋餘觸夢, [1.3, 7.1]) 更多	-	2010-05-20
ASCO2010	N/A	转移性黑色素瘤	22	MPC-6827	(鏇範憲積網簾蓋積鹹觸) = 遞構網餘鏇網憲窪襯衊壓遞選觸選齋夢糧壓鹹 (淵築襯鏇鬱選淵簾鑰淵, [1.7, 5.5])	-	2010-05-20
AACR2009	临床1期	实体瘤	48	Azixa	(醖夢顧願鏇淵夢憲選夢) = 鹽窪艱蓋繭構網糧鑰鑰醖衊願鑰鏇鬱廠範膚鬱 (鹹鏇憲選製餘顧網簾顧 )	-	2009-05-01
ASCO2007	临床1期	HR阳性/HER2低表达实体瘤 \| 脑转移瘤	-	MPC-6827	(衊淵鏇餘選鹽顧鏇窪範) = 顧艱醖製醖醖鏇製齋觸願獵觸夢觸鹽艱餘鑰網 (夢窪醖獵觸觸構顧鹹壓 )	-	2007-06-20