A Phase 2 Study of AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin) in Adult Patients With Recurrence of Glioblastoma Multiforme (GBM) or Gliosarcoma

The primary objective of this study is to determine the 6-month Progression free survival (PFS) when intravenous (IV) AR-67 is administered in adults with confirmed recurrence of GBM who have not recently (> 90 days) recurred after treatment bevacizumab (including patients who've received temazolamide, but no bevacizumab). The primary objective in the rapid bevacizumab failure group (< 90 days) is to determine the 2-month PFS.

开始日期2009-12-01

申办/合作机构

Arno Therapeutics, Inc.

NCT00956787 / Unknown status临床2期

Phase 2 Study of AR-67 (DB-67) in Myelodysplastic Syndrome(MDS)

The purpose of this study is to determine if AR-67 is effective in the treatment for patients with MDS.

开始日期2009-06-01

申办/合作机构

Arno Therapeutics, Inc.

NCT00389480 / Completed临床1期

A Phase I Study of DB-67 (7-t-butyldimethylsilyl-10-hydroxycamptothecin) in Adult Patients With Refractory or Metastatic Solid Malignancies

Hypothesis:
AR-67 (formerly DB-67) represents a rationally engineered drug that possesses improved stability, toxicity, and efficacy compared to current Food and Drug Administration (FDA)-approved camptothecins, based on the extensive research of prior studies. Therefore, the investigators hypothesize that AR-67 (formerly DB-67) will be well-tolerated and efficacious in phase I clinical trials. This initial phase I trial will establish the maximum tolerated dose in humans, establish the toxicity profile, and define the appropriate dose of AR-67 (formerly DB-67) for future phase II and III clinical trials.

开始日期2006-10-01

申办/合作机构

Arno Therapeutics, Inc.

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100 项与 AR-67 相关的临床结果

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100 项与 AR-67 相关的转化医学

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100 项与 AR-67 相关的专利（医药）

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项与 AR-67 相关的文献（医药）

2023-08-13·Microorganisms

Screening and Identification of a Streptomyces Strain with Quorum-Sensing Inhibitory Activity and Effect of the Crude Extracts on Virulence Factors of Pseudomonas aeruginosa.

Article

作者: Gu, Meiying ; Bai, Xiaoyu ; Zhu, Liying ; Zhu, Yanlei ; Yi, Yuanyang ; Sun, Yang ; Zhu, Jing ; Jiang, Ling ; Zhang, Zhidong

Quorum-sensing (QS) is involved in numerous physiological processes in bacteria, such as biofilm formation, sporulation, and virulence formation. Therefore, the search for new quorum-sensing inhibitors (QSI) is a promising strategy that opens up a new perspective for controlling QS-mediated bacterial pathogens. To explore new QSIs, a strain named Streptomyces sp. D67 with QS inhibitory activity was isolated from the soil of the arid zone around the Kumutag Desert in Xinjiang. Phylogenetic analyses demonstrated that strain D67 shared the highest similarity with Streptomyces ardesiacus NBRC 15402T (98.39%), which indicated it represented a potential novel species in the Streptomyces genus. The fermentation crude extracts of strain D67 can effectively reduce the violacein production produced by Chromobacterium violaceum CV026 and the swarming and swimming abilities of Pseudomonas aeruginosa. It also has significant inhibitory activity on the production of virulence factors such as biofilm, pyocyanin, and rhamnolipids of P. aeruginosa in a significant concentration-dependent manner, but not on protease activity. A total of 618 compounds were identified from the fermentation crude extracts of strain D67 by LC-MS, and 19 compounds with significant QS inhibitory activity were observed. Overall, the strain with QS inhibitory activity was screened from Kumutag Desert in Xinjiang for the first time, which provided a basis for further research and development of new QSI.

2020-02-01·Autophagy

Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA)

Article

作者: Ramsden, David Boyer ; Lam, Colin Siu-Chi ; Ho, Shu-Leong ; Liu, Huifang ; Pang, Shirley Yin-Yu ; Ho, Philip Wing-Lok ; Xian, Jiawen ; Leung, Chi-Ting ; Li, Lingfei ; Kung, Michelle Hiu-Wai

Parkinson disease (PD) is an age-related neurodegenerative disorder associated with misfolded SNCA/α-synuclein accumulation in brain. Impaired catabolism of SNCA potentiates formation of its toxic oligomers. LRRK2 (leucine-rich repeat kinase-2) mutations predispose to familial and sporadic PD. Mutant LRRK2 perturbs chaperone-mediated-autophagy (CMA) to degrade SNCA. We showed greater age-dependent accumulation of oligomeric SNCA in striatum and cortex of aged LRRK2^R1441G knockin (KI) mice, compared to age-matched wildtype (WT) by 53% and 31%, respectively. Lysosomal clustering and accumulation of CMA-specific LAMP2A and HSPA8/HSC70 proteins were observed in aged mutant striatum along with increased GAPDH (CMA substrate) by immunohistochemistry of dorsal striatum and flow cytometry of ventral midbrain cells. Using our new reporter protein clearance assay, mutant mouse embryonic fibroblasts (MEFs) expressing either SNCA or CMA recognition 'KFERQ'-like motif conjugated with photoactivated-PAmCherry showed slower cellular clearance compared to WT by 28% and 34%, respectively. However, such difference was not observed after the 'KFERQ'-motif was mutated. LRRK2 mutant MEFs exhibited lower lysosomal degradation than WT indicating lysosomal dysfunction. LAMP2A-knockdown reduced total lysosomal activity and clearance of 'KFERQ'-substrate in WT but not in mutant MEFs, indicating impaired CMA in the latter. A CMA-specific activator, AR7, induced neuronal LAMP2A transcription and lysosomal activity in MEFs. AR7 also attenuated the progressive accumulation of both intracellular and extracellular SNCA oligomers in prolonged cultures of mutant cortical neurons (DIV21), indicating that oligomer accumulation can be suppressed by CMA activation. Activation of autophagic pathways to reduce aged-related accumulation of pathogenic SNCA oligomers is a viable disease-modifying therapeutic strategy for PD.Abbreviations: 3-MA: 3-methyladenine; AR7: 7-chloro-3-(4-methylphenyl)-2H-1,4-benzoxazine; CMA: chaperone-mediated autophagy; CQ: chloroquine; CSF: cerebrospinal fluid; DDM: n-dodecyl β-D-maltoside; DIV: days in vitro; ELISA: enzyme-linked immunosorbent assay; FACS: fluorescence-activated cell sorting; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GWAS: genome-wide association studies; HSPA8/HSC70: heat shock protein 8; KFERQ: CMA recognition pentapeptide; KI: knockin; LAMP1: lysosomal-associated membrane protein 1; LAMP2A: lysosomal-associated membrane protein 2A; LDH: lactate dehydrogenase; LRRK2: leucine-rich repeat kinase 2; MEF: mouse embryonic fibroblast; NDUFS4: NADH:ubiquinone oxidoreductase core subunit S4; NE: novel epitope; PD: Parkinson disease; RARA/RARα: retinoic acid receptor, alpha; SNCA: synuclein, alpha; TUBB3/TUJ1: tubulin, beta 3 class III; WT: wild-type.

2019-09-01·Biopharmaceutics & drug disposition4区 · 医学

Pharmacokinetic modeling of the blood‐stable camptothecin analog AR‐67 in two different formulations

4区 · 医学

Article

作者: Tang, Fei ; Liu, Xiaoxi ; Leggas, Markos ; Adane, Eyob

Abstract:

AR‐67 is a lipophilic camptothecin analog currently under clinical investigation using a Cremophor EL based formulation. However, as potential toxicity limitations exist in the clinical use of Cremophor, an alternative cyclodextrin (SBE‐β‐CD) based formulation has been proposed. Pharmacokinetic (PK) studies were conducted in mice and the SBE‐β‐CD based formulation was compared with the Cremophor EL formulation. PK studies were conducted following intravenous or oral administration of AR‐67 in either Cremophor or SBE‐β‐CD formulation in mice. Noncompartmental analysis was used to determine the plasma and tissue drug distribution. A non‐linear mixed effects (population) PK model was developed to fit both the oral and intravenous data and to estimate key PK parameters. The effect of formulation was explored as a covariate in the PK model. AR‐67 in the SBE‐β‐CD formulation had similar plasma PK and biodistribution to that in the Cremophor EL formulation. The proposed two‐compartment model described the plasma PK of AR‐67 in both formulations adequately. AR‐67 in the SBE‐β‐CD formulation exhibited dose linearity following both oral and intravenous administration. Our studies indicate that SBE‐β‐CD is a viable alternative to Cremophor EL as a pharmaceutical excipient for formulating AR‐67.

项与 AR-67 相关的新闻（医药）

2021-05-03

·BioSpace

Vivacitas Oncology and IAG Partner to Integrate Novel Imaging Markers in the Development of AR-67 in Recurrent Glioblastoma Patients

WALNUT CREEK, CA and LONDON, UK / ACCESSWIRE / May 3, 2021 / Vivacitas Oncology, Inc. ("Vivacitas" or the "Company"), a clinical stage biopharmaceutical company focused on tough to treat cancers, and Image Analysis Group ("IAG"), a leading global medical imaging company, are collaborating to apply Artificial Intelligence (AI) technology and advanced imaging strategies to further the development of AR-67, a third generation Camptothecin, in patients with recurrent glioblastoma multiforme (reGBM). Advanced imaging techniques could play a critical role in response assessment in developing new and innovative cancer therapies. Multiparametric magnetic resonance imaging (mpMRI) provides quantitative non-invasive imaging markers of early therapy-related changes. IAG is deploying its proprietary, cloud-based imaging approach to provide scientific evidence of early therapy response. Tina Runk, Vivacitas co-founder and Executive Vice President of Clinical Operations stated, "Working with IAG, we performed a retrospective analysis of imaging data from our Phase 2 clinical study of AR-67 activity in recurrent GBM, in which their technology was applied to assess pseudoprogression from true progression of disease. This assessment capability demonstrates the benefit of potentially including this technology in future pivotal clinical trials and treatment regimens to ensure patient retention based on more detailed and objective criteria." Dr. Diana Dupont-Roettger, the Chief Scientific Alliance Officer at IAG stated, "We are excited to bring the latest and most impactful imaging strategies to Vivacitas to ensure a scientific excellence and efficient drug development process." ABOUT VIVACITAS ONCOLOGY: Vivacitas Oncology is a private clinical stage biopharmaceutical company focused on combating those cancers that have proven to be frustratingly resistant to current treatment modalities. It originated with the vision of Dr. Joseph Rubinfeld (co-founder of Amgen) with the intent to improve upon well known chemotherapies with demonstrated effect, but which also possess challenges with potency, toxicity, stability, and other issues limiting their use. Through an enduring spirit, Vivacitas continues to apply clarity, tenacity, and vision in our fight against intractable cancers and our pursuit of new treatment options for patients and their families worldwide. For further information please visit or Elise@vivaoncology.com. ABOUT IAG: Image Analysis Group (IAG) is a unique clinical development partner to life sciences companies. IAG broadly leverages its proprietary image analysis methodologies, power of our cloud platform DYNAMIKA, years of experience in AI and Machine Learning as well as bespoke co-development business models to ensure higher probability for promising therapeutics to reach the patients. Our independent Bio-Partnering division fuses risk-sharing business models and agile culture to accelerate novel drug development. For further information please visit or reach out to imaging.experts@ia-grp.com. SOURCE: Vivacitas Oncology, Inc. View source version on accesswire.com:

100 项与 AR-67 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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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
多形性胶质母细胞瘤	临床2期	美国	Arno Therapeutics, Inc.	2009-12-01
多形性胶质母细胞瘤	临床2期	加拿大	Arno Therapeutics, Inc.	2009-12-01
神经胶质肉瘤	临床2期	美国	Arno Therapeutics, Inc.	2009-12-01
神经胶质肉瘤	临床2期	加拿大	Arno Therapeutics, Inc.	2009-12-01
转移性实体瘤	临床1期	美国	Arno Therapeutics, Inc.	2006-10-01