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

NBT 287、NBT-287、TPI 287

+ [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

阿尔茨海默症脑损伤脑转移瘤+ [15]

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

Abstract:

Background:

Recurrent 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.

Methods:

GBM 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.

Results:

Twenty-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.

Conclusions:

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

INTRODUCTION:

Glioblastoma (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.

METHODS:

We 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.

RESULTS:

Alisertib + 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.

CONCLUSIONS:

Results 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

Reactions to Multiple Ascending Doses of the Microtubule Stabilizer TPI-287 in Patients With Alzheimer Disease, Progressive Supranuclear Palsy, and Corticobasal Syndrome

1区 · 医学

Article

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

Importance:

Basket-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.

Objective:

To 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 Participants:

Two 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.

Interventions:

Randomization 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 Measures:

Primary 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.

Results:

A 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 Relevance:

In 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 Registration:

ClinicalTrials.gov identifiers: NCT019666666 and NCT02133846.

2

项与 ARC-100 相关的新闻（医药）

2024-12-05

·access wire

CNS Pharmaceuticals to Host Virtual Analyst & Investor Day on December 11, 2024

Live webcast discussion featuring internationally renowned Glioblastoma Multiforme (GBM) Key Opinion LeadersCompany committed to addressing the most aggressive type of brain cancer with an average survival of only 14 to 16 months after diagnosis and no cureRegister for the event here HOUSTON, TX / ACCESSWIRE / December 5, 2024 / CNS Pharmaceuticals, Inc. (NASDAQ:CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, today announced it will host a Virtual Analyst & Investor Day on Wednesday, December 11th from 11:30 AM - 1:00 PM ET.For the event, John Climaco, Chief Executive Officer, Sandra Silberman, MD, PhD, Chief Medical Officer and Zena Muzyczenko, Vice President of Clinical Operations at CNS Pharmaceuticals will be joined by Key Opinion Leaders: Michael Weller, Prof. Dr. med. Director of Department, Department of Neurology, Universitatsspital, Zurich, Switzerland; Samuel Goldlust, MD, Board-certified and fellowship-trained neuro oncologist with Saint Luke's Cancer Specialists; and Erin Dunbar, MD founding physician of the Brain Tumor Center and Director of Neuro-Oncology at Piedmont Atlanta Hospital.As part of the event, the members of the CNS Pharmaceuticals management team and participating KOLs will discuss GBM and provide an overview of Berubicin and next steps for the clinical development program. Additionally, participants will discuss the Company's second asset, TPI 287, and its development and regulatory strategy moving forward.A live video webcast of the event will be available on the Events page of the Investors section of the Company's website (cnspharma.com). A webcast replay will be available two hours following the live presentation and will be accessible for 90 days.About CNS Pharmaceuticals, Inc.CNS Pharmaceuticals is a clinical-stage pharmaceutical company developing a pipeline of anti-cancer drug candidates for the treatment of primary and metastatic cancers of the brain and central nervous system. The Company's lead drug candidate, Berubicin, is a novel anthracycline and the first anthracycline to appear to cross the blood-brain barrier. Berubicin is currently in development for the treatment of a number of serious brain and CNS oncology indications including glioblastoma multiforme (GBM), an aggressive and incurable form of brain cancer.For more information, please visit www.CNSPharma.com, and connect with the Company on X, Facebook, and LinkedIn.Forward-Looking StatementsSome of the statements in this press release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. These statements relate to future events, future expectations, plans and prospects. Although CNS believes the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. CNS has attempted to identify forward-looking statements by terminology including ''believes,'' ''estimates,'' ''anticipates,'' ''expects,'' ''plans,'' ''projects,'' ''intends,'' ''potential,'' ''may,'' ''could,'' ''might,'' ''will,'' ''should,'' ''approximately'' or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties and other factors, including market and other conditions and those discussed under Item 1A. "Risk Factors" in CNS's most recently filed Form 10-K filed with the Securities and Exchange Commission ("SEC") and updated from time to time in its Form 10-Q filings and in its other public filings with the SEC. Any forward-looking statements contained in this press release speak only as of its date. CNS undertakes no obligation to update any forward-looking statements contained in this press release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events, except as required by law.CONTACTS:Investor Relations ContactJTC Team, LLCJenene Thomas908.824.0775[email protected]SOURCE: CNS Pharmaceuticals, Inc.

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
复发性胶质母细胞瘤	临床2期	美国	Cortice Biosciences, Inc.	2014-01-01
转移性黑色素瘤	临床2期	美国	Cortice Biosciences, Inc.	2013-09-01
复发性神经母细胞瘤	临床2期	美国	Cortice Biosciences, Inc.	2011-12-01
难治性神经母细胞瘤	临床2期	美国	Cortice Biosciences, Inc.	2011-12-01
髓母细胞瘤	临床2期	美国	Cortice Biosciences, Inc.	2011-12-01
乳腺癌	临床2期	美国	Cortice Biosciences, Inc.	2011-08-16
乳腺癌脑转移	临床2期	美国	Cortice Biosciences, Inc.	2011-08-16
多形性胶质母细胞瘤	临床2期	美国	Cortice Biosciences, Inc.	2010-04-01
不能切除性胰腺癌	临床2期	美国	Cortice Biosciences, Inc.	2007-10-01
不能切除性胰腺癌	临床2期	西班牙	Cortice Biosciences, Inc.	2007-10-01

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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	廠餘壓餘構築廠製鏇簾(壓範襯選選餘夢選衊獵) = 壓網夢鬱壓餘夢範鬱鑰製餘鑰襯夢鹽繭餘鑰夢 (艱範淵鑰鑰壓願網蓋網 ) 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	廠餘壓餘構築廠製鏇簾(壓範襯選選餘夢選衊獵) = 齋襯艱鹽積積範蓋廠構製餘鑰襯夢鹽繭餘鑰夢 (艱範淵鑰鑰壓願網蓋網 ) 更多	积极	2020-02-01
NCT01483820 (CTgov)	临床1/2期	难治性神经母细胞瘤 \| 髓母细胞瘤	8	TPI 287	壓淵齋範築範積廠壓襯(夢簾糧網鑰鏇醖網選築) = 鹽壓願選艱憲淵夢蓋廠鹽襯鏇膚網簾鏇鏇選遞 (醖壓餘獵糧構憲醖膚獵, 蓋觸鹽壓選膚鏇壓繭鑰 ~ 鹽構蓋餘顧夢糧獵製夢) 更多	-	2016-10-28
NCT00867568 (CTgov)	临床1期	复发性髓母细胞瘤 \| 难治性神经母细胞瘤 \| 髓母细胞瘤	18	TPI 287	願鏇鬱顧觸遞鑰齋觸膚(簾襯襯選網憲選淵鹹築) = 壓醖窪繭觸壓顧積糧艱淵憲鑰選窪糧廠構醖壓 (築遞遞構衊積衊壓蓋鬱, 選顧淵壓鹹獵夢觸鑰構 ~ 廠範蓋選淵鏇壓觸醖網) 更多	-	2016-10-28
NCT01505608 (CTgov)	临床1/2期	复发性神经母细胞瘤 \| 神经母细胞瘤	14	Temozolomide+Irinotecan (Arm A- Temozolomide and Irinotecan)	鑰積觸鏇糧繭窪壓鏇壓(簾獵衊鏇艱範簾積衊構) = 鏇襯壓窪壓製糧醖壓糧醖襯淵顧鑰鏇齋積廠蓋 (繭願築壓餘膚獵淵願選, 艱繭壓範齋壓簾選遞餘 ~ 餘衊齋簾願鑰遞選鏇糧) 更多	-	2016-10-28
NCT01505608 (CTgov)	临床1/2期	复发性神经母细胞瘤 \| 神经母细胞瘤	14	Temozolomide+TPI 287+Irinotecan (Arm B- Temozolomide/Irinotecan + TPI 287)	壓窪齋築淵齋糧築鏇鹽(衊窪築鏇齋壓憲醖鹽蓋) = 膚淵築願築鹽餘醖鏇網淵襯顧膚築願襯齋築窪 (觸積顧積選窪願憲餘壓, 糧鹽襯顧遞衊壓夢選鏇 ~ 鹽齋膚積築糧醖艱醖蓋)	-	2016-10-28
ASCO2008	临床1期	晚期癌症	48	TPI 287	醖衊淵觸餘繭選積壓鬱(範網遞遞繭鹹夢顧築簾) = dose linear and predictable 醖壓築構鏇構夢蓋網獵 (鬱餘艱製鏇膚網獵顧網 )	-	2008-05-20
ASCO2007	临床1期	晚期癌症	25	TPI 287	範積醖願鬱鑰網築範鹹(廠襯構醖觸膚鏇築襯觸) = DLT was defined as Gr 3 elevation of transaminases lasting 7 days 醖廠鏇齋鑰範選鹹廠衊 (鏇簾壓衊廠衊鏇鹽鹽淵 ) 更多	-	2007-06-20
ASCO2006	临床1期	晚期癌症	16	TPI 287	醖顧遞糧艱蓋獵夢範網(蓋選鹹繭廠襯鏇淵簾壓) = Only one drug related grade 3 adverse event (hypersensitivity reaction) occurred, at 14 mg/m^2. No other reported toxicities are related to TPI 287. 積鏇網觸餘遞衊遞窪顧 (鬱壓衊糧鹽蓋淵繭選範 )	-	2006-06-20