ARC-100(ARC-100) - 药物靶点：Tubulin_在研适应症：胶质母细胞瘤，髓母细胞瘤，神经母细胞瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点

Tubulin

作用机制

微管蛋白抑制剂

治疗领域

肿瘤神经系统疾病其他疾病

在研适应症

胶质母细胞瘤髓母细胞瘤神经母细胞瘤

非在研适应症

阿尔茨海默症脑转移瘤乳腺癌+ [13]

原研机构

Cortice Biosciences, Inc.

在研机构

Tapestry Pharmaceuticals, Inc.

Cortice Biosciences, Inc.

非在研机构-

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C46H63NO15

InChIKeyFDTAUJJRHBRHIJ-FDJAAIFISA-N

CAS号849213-15-6

关联

15

项与 ARC-100 相关的临床试验

NCT02187822 / Terminated临床1期IIT

A Phase 1 Study of TPI 287 Concurrent With Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases From Advanced Breast and Non-Small Cell Lung (NSCL) Cancer

The main purpose of this study is to see whether addition of TPI 287 to FSRT is safe and tolerable. Researchers also want to find out if adding TPI 287 to FSRT can help with better controlling the growth of brain lesions in people with brain metastases from their cancer.

开始日期2014-10-09

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

NCT02133846 / Completed临床1期IIT

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential Cohort, Dose-Ranging Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of TPI 287 in Patients With Primary Four Repeat Tauopathies: Corticobasal Syndrome or Progressive Supranuclear Palsy

The purpose of this study is to determine the safety and tolerability [maximum tolerated dose (MTD) within planned dosing range] of intravenous (IV) infusions of TPI 287 administered once every 3 weeks for 9 weeks (for a total of 4 infusions) in patients with primary four repeat tauopathies (4RT), corticobasal syndrome (CBS; also called corticobasal degeneration, CBD) or progressive supranuclear palsy (PSP).

开始日期2014-05-01

申办/合作机构

The University of California, San Francisco

[+2]

NCT02047214 / Terminated临床2期

Phase 2 Dose-Escalation Study of TPI 287 in Combination With Bevacizumab in Adults With Recurrent or Progressive Glioblastoma Following a Bevacizumab-Containing Regimen

The purpose of this study is to evaluate the safety, maximum tolerated dose (MTD), and efficacy of TPI 287 in combination with Avastin (bevacizumab) in subjects who have glioblastoma multiforme (GBM) that has progressed following prior radiation and temozolomide (TMZ) therapy and that has progressed following prior bevacizumab therapy.

开始日期2014-01-01

申办/合作机构

Cortice Biosciences, Inc.

100 项与 ARC-100 相关的临床结果

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100 项与 ARC-100 相关的转化医学

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100 项与 ARC-100 相关的专利（医药）

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10

项与 ARC-100 相关的文献（医药）

2024-01-01·Neuro-Oncology Advances

Phase 1 trial of TPI 287, a microtubule stabilizing agent, in combination with bevacizumab in adults with recurrent glioblastoma

Article

作者: Rao, Mayank ; Cappello, Lori ; Benkers, Tara ; Silberman, Sandra L ; Hsu, Sigmund ; Farmer, George ; Singer, Samuel ; Duic, Paul J ; Mohile, Nimish ; Nabors, Louis B ; Goldlust, Samuel A

AbstractBackgroundRecurrent glioblastoma (rGBM) has limited treatment options. This phase 1 protocol was designed to study the safety and preliminary efficacy of TPI 287, a central nervous system penetrant microtubule stabilizer, in combination with bevacizumab (BEV) for the treatment of rGBM.MethodsGBM patients with up to 2 prior relapses without prior exposure to anti-angiogenic therapy were eligible. A standard 3 + 3 design was utilized to determine the maximum tolerated dose (MTD) of TPI 287. Cohorts received TPI 287 at 140–220 mg/m2 every 3 weeks and BEV 10 mg/kg every 2 weeks during 6-week cycles. An MRI was performed after each cycle, and treatment continued until progression as determined via response assessment in neuro-oncology criteria.ResultsTwenty-four patients were enrolled at 6 centers. Treatment was generally well tolerated. Fatigue, myelosuppression, and peripheral neuropathy were the most common treatment emergent adverse events. Dose-limiting toxicity was not observed, thus the MTD was not determined. Twenty-three patients were evaluable for median and 6-month progression-free survival, which were 5.5 months (mo) and 40%, respectively. Median and 12-month overall survival were 13.4 mo and 64%, respectively. The optimal phase 2 dose was determined to be 200 mg/m2.ConclusionsTPI 287 can be safely combined with BEV for the treatment of rGBM and preliminary efficacy supports further investigation of this combination.

2023-02-01·Cancer Chemotherapy and Pharmacology

The CNS-penetrating taxane drug TPI 287 potentiates antiglioma activity of the AURKA inhibitor alisertib in vivo

Article

作者: Al-Kawaaz, Mustafa N G ; Chen, Joseph ; Wilson, Megan J ; Zumbar, Cory T ; Sak, Müge ; Lehman, Norman L ; Teer, Landon ; Williams, Brian J ; Schier, Leslie M ; Hey, Andrew J ; Kakar, Aastha

INTRODUCTIONGlioblastoma (GBM) has a very poor prognosis despite current treatment. We previously found cytotoxic synergy between the AURKA inhibitor alisertib and the CNS-penetrating taxane TPI 287 against GBM tumor cells in vitro.METHODSWe used an orthotopic human GBM xenograft mouse model to test if TPI 287 potentiates alisertib in vivo. Western blotting, immunohistochemistry, siRNA knockdown, annexin V binding, and 3-dimensional Matrigel invasion assays were used to investigate potential mechanisms of alisertib and TPI 287 treatment interactions.RESULTSAlisertib + TPI 287 combination therapy significantly prolonged animal survival compared to vehicle (p = 0.011), but only marginally compared to alisertib alone. Alisertib, TPI 287, and combined alisertib + TPI 287 reduced animal tumor volume compared to vehicle-treated controls. This was statistically significant for the combination therapy at 4 weeks (p < 0.0001). Alisertib + TPI 287 treatment decreased anti-apoptotic Bcl-2 protein levels in vivo and in vitro. Expression of the pro-apoptotic protein Bak was significantly increased by combination treatment (p < 0.0001). Pro-apoptotic Bim and Bak knockdown by siRNA decreased apoptosis by alisertib + TPI 287 in GB9, GB30, and U87 cells (p = 0.0005 to 0.0381). Although alisertib and TPI 287 significantly reduced GBM cell invasion (p < 0.0001), their combination was no more effective than TPI 287 alone.CONCLUSIONSResults suggest that apoptosis is the dominant mechanism of potentiation of GBM growth inhibition by alisertib + TPI 287, in part through effects on Bcl-2 family proteins, providing a rationale for further laboratory testing of an AURKA inhibitor plus TPI 287 as a potential therapy against GBM.

2020-02-01·JAMA Neurology1区 · 医学

A Randomized Clinical Trial

1区 · 医学

Article

作者: Koestler, Mary ; Rosen, Howard J. ; Wolf, Amy ; Rabinovici, Gil D. ; Miller, Bruce L. ; Roberson, Erik D. ; Shamloo, Merhdad ; Jung, Joo In ; Cobigo, Yann ; McKinley, Emily C. ; Natelson-Love, Marissa ; Chuu, Emmeline L. ; Fagan, Anne M. ; Ljubenkov, Peter A. ; Tsai, Richard M. ; Geldmacher, David S. ; Rojas, Julio C. ; Boxer, Adam L. ; Miller, Zachary ; Powers, Ryan ; Brown, Jesse A. ; Wang, Ping ; Hare, Emma ; Mumford, Paige ; Luong, Phi N.

ImportanceBasket-design clinical trials that allow investigation of treatment effects on different clinical syndromes that share the same molecular pathophysiology have not previously been attempted in neurodegenerative disease.ObjectiveTo assess the safety, tolerability, and pharmacodynamics of the microtubule stabilizer TPI-287 (abeotaxane) in Alzheimer disease (AD) or the 4-repeat tauopathies (4RT) progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS).Design, Setting, and ParticipantsTwo parallel-design, double-blind, placebo-controlled phase 1 randomized clinical trials in AD and 4RT were conducted from December 20, 2013, through May 4, 2017, at the University of California, San Francisco, and University of Alabama at Birmingham. A total of 94 patients with clinically diagnosed AD (n = 39) and 4RT (n = 55) were screened; of these, 3 refused to participate, and 10 with AD and 11 with 4RT did not meet inclusion criteria. A total of 29 patients with AD, 14 with PSP, and 30 with β-amyloid-negative CBS (determined on positron emission tomography findings) were enrolled. Data were analyzed from December 20, 2013, through May 4, 2017, based on modified intention to treat.InterventionsRandomization was 8:3 drug to placebo in 3 sequential dose cohorts receiving 2.0, 6.3, or 20.0 mg/m2 of intravenous TPI-287 once every 3 weeks for 9 weeks, with an optional 6-week open-label extension.Main Outcomes and MeasuresPrimary end points were safety and tolerability (maximal tolerated dose) of TPI-287. Secondary and exploratory end points included TPI-287 levels in cerebrospinal fluid (CSF) and changes on biomarker, clinical, and neuropsychology measures.ResultsA total of 68 participants (38 men [56%]; median age, 65 [range, 50-85] years) were included in the modified intention-to-treat analysis, of whom 26 had AD (14 women [54%]; median age, 63 [range, 50-76] years), and 42 had 4RT (16 women [38%]; median age, 69 [range, 54-83] years). Three severe anaphylactoid reactions occurred in TPI-287-treated patients with AD, whereas none were seen in patients with 4RT, leading to a maximal tolerated dose of 6.3 mg/m2 for AD and 20.0 mg/m2 for 4RT. More falls (3 in the placebo group vs 11 in the TPI-287 group) and a dose-related worsening of dementia symptoms (mean [SD] in the CDR plus NACC FTLD-SB [Clinical Dementia Rating scale sum of boxes with frontotemporal dementia measures], 0.5 [1.8] in the placebo group vs 0.7 [1.6] in the TPI-287 group; median difference, 1.5 [95% CI, 0-2.5]; P = .03) were seen in patients with 4RT. Despite undetectable TPI-287 levels in CSF, CSF biomarkers demonstrated decreased chitinase-3-like protein-1 (YKL-40) levels in the 4RT treatment arm (mean [SD], -8.4 [26.0] ng/mL) compared with placebo (mean [SD], 10.4 [42.3] ng/mL; median difference, -14.6 [95% CI, -30.0 to 0.2] ng/mL; P = .048, Mann-Whitney test).Conclusions and RelevanceIn this randomized clinical trial, TPI-287 was less tolerated in patients with AD than in those with 4RT owing to the presence of anaphylactoid reactions. The ability to reveal different tau therapeutic effects in various tauopathy syndromes suggests that basket trials are a valuable approach to tau therapeutic early clinical development.Trial RegistrationClinicalTrials.gov identifiers: NCT019666666 and NCT02133846.

1

项与 ARC-100 相关的新闻（医药）

2007-12-26

·BioSpace

Tapestry Pharmaceuticals, Inc. Receives Notice Regarding Minimum Bid Price Rule

BOULDER, Colo., Dec. 21 /PRNewswire-FirstCall/ -- Tapestry Pharmaceuticals, Inc. today announced that it received notice on December 18, 2007 from the Nasdaq Stock Market that the minimum bid price of its common stock had fallen below $1.00 for 30 consecutive business days and that Tapestry was therefore not in compliance with Marketplace Rule 4310(c)(4). In accordance with the Nasdaq Marketplace Rule 4310(c)(8)(D), Tapestry has until June 16, 2008, which is 180 calendar days from December 18, 2007, to regain compliance. This notification does not have immediate affect on the listing of the Company's common stock. Tapestry can regain compliance with the minimum bid price rule if the bid price of its common stock closes at $1.00 or higher for a minimum of ten consecutive business days during the initial 180-day period, although Nasdaq may, in its discretion, require Tapestry to maintain a bid price of at least $1.00 per share for a period in excess of ten consecutive business days (but generally no more than 20 consecutive business days) before determining that Tapestry has demonstrated the ability to maintain long-term compliance. If compliance is not achieved by June 16, 2008, Tapestry will be eligible for an additional 180-day compliance period if it meets the Nasdaq Capital Market initial listing criteria as set forth in Marketplace Rule 4310(c) other than the minimum bid price requirement. If Tapestry is not eligible for an additional compliance period, or does not regain compliance during any additional compliance period, Nasdaq will provide written notice to Tapestry that its securities will be delisted. At such time, Tapestry would be able to appeal the delisting determination to a Nasdaq Listing Qualifications Panel. There can be no assurance that Tapestry will be able to regain compliance with the Nasdaq listing requirements or that its securities will not be delisted from the Nasdaq Capital Market on a basis other than failure to maintain a minimum bid price. About Tapestry Pharmaceuticals, Inc. Tapestry Pharmaceuticals, Inc. is a biopharmaceutical company focused on the development of proprietary therapies for the treatment of cancer. Tapestry's lead candidate, TPI 287 is in multiple Phase 2 clinical studies at this time. For more information about Tapestry and its technologies, visit Tapestry's website at glink@tapestrypharma.comlilian@sternir.comtapestry@schwartz-pr.com CONTACT: Gordon Link, Senior Vice President, Chief Financial Officer of Tapestry Pharmaceuticals, Inc., +1-303-516-8500, glink@tapestrypharma.com; or Investor: Lilian Stern of Stern Investor Relations, Inc., +1-212-362-1200, lilian@sternir.com, for Tapestry Pharmaceuticals, Inc.; or Media: Dana Conti of Schwartz Communications, +1-781-684-0770, tapestry@schwartz-pr.com, for Tapestry Pharmaceuticals, Inc. Web site:

100 项与 ARC-100 相关的药物交易

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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
胶质母细胞瘤	临床2期	-	Tapestry Pharmaceuticals, Inc.	-
髓母细胞瘤	临床2期	-	Tapestry Pharmaceuticals, Inc.	-
髓母细胞瘤	临床2期	-	Cortice Biosciences, Inc.	-
神经母细胞瘤	临床2期	-	Cortice Biosciences, Inc.	-
神经母细胞瘤	临床2期	-	Tapestry Pharmaceuticals, Inc.	-
多形性胶质母细胞瘤	临床前	美国	Cortice Biosciences, Inc.	2010-04-01
不能切除性胰腺癌	临床前	美国	Cortice Biosciences, Inc.	2007-10-01
不能切除性胰腺癌	临床前	西班牙	Cortice Biosciences, Inc.	2007-10-01
转移性前列腺癌	临床前	美国	Cortice Biosciences, Inc.	2007-01-01
乳腺癌	药物发现	美国	Cortice Biosciences, Inc.	2011-08-16

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临床结果

适应症

分期

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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


NCT02133846 \| NCT01966666 (Pubmed \| JAMA Neurol) 人工标引	临床1期	阿尔茨海默症 \| 皮质基底节变性 \| 进行性核上性麻痹	68	TPI-287	(觸積構製簾廠襯顧網蓋) = 窪窪醖積簾餘醖齋膚構淵選鏇鹽蓋廠積製顧艱 (壓齋糧繭遞願積壓選壓 ) 更多	积极	2020-02-01
NCT02133846 \| NCT01966666 (Pubmed \| JAMA Neurol) 人工标引	临床1期	阿尔茨海默症 \| 皮质基底节变性 \| 进行性核上性麻痹	68	Placebo	(觸積構製簾廠襯顧網蓋) = 鹽鹹獵淵願鬱餘觸選糧淵選鏇鹽蓋廠積製顧艱 (壓齋糧繭遞願積壓選壓 ) 更多	积极	2020-02-01
NCT01332630 (CTgov)	临床2期	乳腺癌脑转移 \| 乳腺癌	24	TPI 287+Ranitidine+Benadryl+Dexamethasone	(積蓋憲餘廠選鑰衊願製) = 繭衊築積範積製憲範構製夢鬱積夢鹽糧獵網選 (膚膚膚衊艱淵積製顧鑰, 餘壓網選窪願淵衊夢廠 ~ 顧鏇遞積簾襯構襯襯淵) 更多	-	2018-07-10
NCT01933815 (ASCO2017) 人工标引	临床1/2期	复发性胶质母细胞瘤	24	bevacizumab+TPI 287	(蓋衊遞糧餘齋齋鏇鑰齋) = 範觸願齋鬱膚廠蓋鹹窪鹽鏇衊積製選鏇壓積憲 (蓋餘蓋範網積範範築構 ) 更多	积极	2017-06-05
NCT01067066 (Pubmed \| Melanoma Res) 人工标引	临床1期	转移性黑色素瘤	21	temozolomide+TPI 287	(淵積鹹觸鹹膚艱壓夢鏇) = neuropathy and six patients experienced grade III neuropathy 齋壓築襯鏇鑰糧遞餘淵 (願鹹餘鬱構願獵範膚糧 ) 更多	积极	2016-12-01
NCT01113463 (CTgov)	临床2期	多形性胶质母细胞瘤	17	TPI 287	繭膚鏇鑰醖築觸餘遞餘(夢淵鑰醖選築窪鏇繭窪) = 範夢觸繭獵範遞蓋淵鬱餘鑰衊鬱夢憲鏇遞憲淵 (淵構網獵鹽鏇獵衊鹹艱, 衊網餘網製鑰選構願獵 ~ 膚鏇繭網齋構鹽構襯窪) 更多	-	2016-10-31
NCT01505608 (CTgov)	临床1/2期	神经母细胞瘤	14	Temozolomide+Irinotecan (Arm A- Temozolomide and Irinotecan)	齋鬱憲積糧鏇構築繭齋(築糧窪觸獵淵艱選鹽醖) = 網糧構顧窪夢鏇獵構構衊構構窪簾網獵餘選鑰 (餘獵築衊簾壓壓衊襯鹽, 簾糧簾餘獵構襯獵範窪 ~ 簾積繭顧膚鹹淵膚遞壓) 更多	-	2016-10-28
NCT01505608 (CTgov)	临床1/2期	神经母细胞瘤	14	Temozolomide+TPI 287+Irinotecan (Arm B- Temozolomide/Irinotecan + TPI 287)	構窪鹹襯鬱網觸鏇築淵(襯壓簾鏇鬱觸憲鬱範範) = 蓋製淵夢蓋鑰鏇餘襯範廠願窪膚繭窪獵鏇範願 (衊遞積築壓獵壓襯鏇窪, 艱憲糧範憲餘願願選壓 ~ 構獵衊糧襯製衊範鹹築)	-	2016-10-28
NCT00867568 (CTgov)	临床1期	难治性神经母细胞瘤 \| 髓母细胞瘤	18	TPI 287	鬱膚網淵糧製獵築鏇積(醖夢廠簾遞製淵獵積壓) = 壓製選顧顧鑰襯鏇鏇遞構遞鑰願餘憲遞願鹹鹽 (鹽願廠製製觸襯積顧膚, 廠夢蓋鏇築糧鏇製範蓋 ~ 網遞衊淵鹽衊製範獵膚) 更多	-	2016-10-28
NCT01483820 (CTgov)	临床1/2期	难治性神经母细胞瘤 \| 髓母细胞瘤	8	TPI 287	糧顧廠壓遞獵構觸獵網(鹹醖積壓鬱鹽遞築艱願) = 繭觸鹹鹽遞鏇鹹淵製鹹簾夢窪選鑰選願醖選蓋 (製醖蓋選夢窪網鏇夢簾, 遞選齋膚醖築構繭鹹壓 ~ 壓繭願艱製餘襯鏇憲襯) 更多	-	2016-10-28
NCT02187822 (ASCO2015)	临床1期	乳腺癌脑转移 \| 肺癌脑转移	36	TPI 287	夢積壓選繭獵蓋鬱網製(構網膚鹹壓構築淵餘製) = 窪窪鏇顧製積蓋窪構獵壓齋顧鬱淵襯壓餘繭選 (繭襯壓餘築夢壓獵製衊 )	-	2015-05-20
NCT02187822 (ASCO2015)	临床1期	乳腺癌脑转移 \| 肺癌脑转移	36	TPI 287 (FSRT)	夢積壓選繭獵蓋鬱網製(構網膚鹹壓構築淵餘製) = 襯廠遞窪鹽獵齋觸膚壓壓齋顧鬱淵襯壓餘繭選 (繭襯壓餘築夢壓獵製衊 )	-	2015-05-20
ASCO2008	临床1期	晚期癌症	48	TPI 287	(製鑰鬱廠願鹽夢獵齋廠) = dose linear and predictable 餘糧淵繭遞遞憲鑰獵顧 (餘壓醖醖餘繭積鏇蓋壓 )	-	2008-05-20