Antineoplaston A10(Antineoplaston A10) - 在研适应症：脑干胶质瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Antineoplaston A 10、Atengenal

+ [1]

靶点-

作用方式

诱导剂

作用机制

细胞凋亡诱导剂

治疗领域

肿瘤神经系统疾病

在研适应症

脑干胶质瘤

非在研适应症

食管腺癌肺腺癌前列腺腺癌+ [43]

原研机构

Burzynski Research Institute, Inc.

在研机构

Burzynski Research Institute, Inc.

非在研机构-

最高研发阶段临床3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/序列

分子式C13H14N2O3

InChIKeyOQGRFQCUGLKSAV-JTQLQIEISA-N

CAS号91531-30-5

关联

64

项与 Antineoplaston A10 相关的临床试验

NCT02864888

/ Not yet recruiting临床3期IIT

A Controlled, Study of the Effect of Combination Antineoplaston Therapy [Atengenal (A10) and Astugenal (AS2-1)] on the QT/QTc Interval In Subjects With Newly Diagnosed Diffuse, Intrinsic, Brainstem Glioma

The primary objective of this protocol study is to investigate the effect of Antineoplaston therapy on the QT/QTc interval in study subjects age 3 to 21 years with newly-diagnosed, diffuse, intrinsic brainstem glioma. This investigation is to be conducted in parallel with a phase 3 efficacy and safety study of combination Antineoplaston therapy + radiation vs. radiation alone (BRI-BT-52).

开始日期2027-06-01

申办/合作机构

Burzynski Research Institute, Inc.

NCT02887040

/ Not yet recruiting临床3期IIT

A Randomized Phase 3 Study of Combination Antineoplaston Therapy [Antineoplastons A10 (Atengenal) and AS2-1 (Astugenal)] Plus Radiation Therapy vs. Radiation Therapy Only in Subjects With Newly Diagnosed Diffuse, Intrinsic, Brainstem Glioma

Patients ≥ 3 years of age with newly-diagnosed, diffuse, intrinsic pontine glioma will be enrolled in this study. However, the primary objectives of this study are to 1) compare overall survival, the time from randomization to death from any cause, for study subjects 3-21 years of age with newly-diagnosed, diffuse, intrinsic pontine glioma who receive Antineoplaston therapy (Atengenal + Astugenal) + radiation therapy vs. radiation therapy alone and 2) describe the toxicity profile (all subjects) for Antineoplaston therapy + radiation therapy vs. radiation therapy alone.
A secondary objective is to compare progression-free survival for study subjects 3-21 years of age with newly-diagnosed, diffuse, intrinsic pontine glioma treated with Antineoplaston therapy + radiation therapy vs. radiation therapy alone.

开始日期2025-06-01

申办/合作机构

Burzynski Research Institute, Inc.

KCT0008386

/ Active, not recruiting临床3期

24 weeks, Randomized, Double blind, Parallel-group, Sham Device-Controlled, Medical Device Pivotal Clinical Study to Evaluate the Efficacy and Safety of HM-SC-10 as Low-Level Light Therapy (LLLT) for Androgenetic Alopecia(AGA)

开始日期2022-08-31

申办/合作机构

Huons Medicare Co., Ltd.

100 项与 Antineoplaston A10 相关的临床结果

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100 项与 Antineoplaston A10 相关的转化医学

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100 项与 Antineoplaston A10 相关的专利（医药）

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86

项与 Antineoplaston A10 相关的文献（医药）

2024-05-03·Toxicology Mechanisms and Methods

Reactions of deoxyribonucleotide bases with sulfooxymethyl or halomethyl polycyclic aromatic hydrocarbons induce unwinding of DNA supercoils

Article

作者: Lehner, Andreas F.

Torsional stress in double-stranded DNA enables and regulates facets of chromosomal metabolism, replication, and transcription and requires regulatory enzymatic systems including topoisomerases and histone methyltransferases. As such, this machinery may be subject to deleterious effects from reactive mutagens, including ones from carcinogenic polycyclic aromatic hydrocarbon (PAH) adduct formation with DNA. Supercoiled plasmid DNA was investigated for its torsional responses to adducts formed in vitro from PAH benzylic carbocation reactive intermediates created spontaneously by release of leaving groups. PAH sulfate esters were found to (1) unwind DNA in a concentration dependent manner, and (2) provide maximum unwinding in a pattern consistent with known carcinogenicities of the parent PAHs, that is, 6-methylbenzo[a]pyrene > 7,12-methylbenz[a]anthracene > 3-methylcholanthrene > 9-methylanthracene > 7-methylbenz[a]anthracene > 1-methylpyrene. Supercoil unwinding was demonstrated to be dependent on the presence of sulfate or chloride leaving groups such that reactive carbocations were generated in situ by hydrolysis. In silico modeling of intercalative complex topology showed PAH benzylic carbocation reactive functional groups in alignment with target nucleophiles on guanine bases in a 5'-dCdG-3' pocket in agreement with known formation of nucleotide adducts. Inhibitory or modulatory effects on PAH-induced supercoil unwinding were seen with ascorbic acid and an experimental antineoplastic agent Antineoplaston A10 in agreement with their known anticarcinogenic properties. In summary, the reactive PAH intermediates studied here undoubtedly participate in well-known mutational mechanisms such as frameshifts and apurinic site generation. However, they are also capable of random disruption of chromosomal supercoiling in a manner consistent with the known carcinogenicities of the parent compounds, and this mechanism may represent an additional detrimental motif worthy of further study for a more complete understanding of chemical carcinogenicity.

2018-08-01·Cancer Biotherapy and Radiopharmaceuticals4区 · 医学

Improved Targeting and Tumor Retention of a Newly Synthesized Antineoplaston A10 Derivative by Intratumoral Administration: Molecular Docking, Technetium 99m Radiolabeling, andIn VivoBiodistribution Studies

4区 · 医学

Article

作者: Ibrahim, Ismail T. ; El-Kolaly, Mohamed T. ; Abdelbary, Aly A. ; Tadros, Mina I. ; Aboumanei, Mohamed H.

BACKGROUNDRecently, the direct intratumoral (i.t.) injection of anticancer agents has been investigated. A newly synthesized Antineoplaston A10 analog 3-(4-methoxybenzoylamino)-2,6-piperidinedione (MPD) showed an antitumor activity in human breast cancer cell line. Unfortunately, MPD suffered from poor water solubility.MATERIALS AND METHODSPseudoternary phase diagram of oil (isopropyl myristate), surfactant (Tween 80), cosurfactant (ethanol), and water was plotted. MPD microemulsion (MPDME) was developed and characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), and morphology (transmission electron microscopy). MPDME and MPD solution (MPDS) were radiolabeled with technetium 99m (^99mTc) using stannous chloride dihydrate (SnCl₂.2H₂O). Molecular docking of MPD and ^99mTc-MPD was performed to study the interaction with DNA.RESULTSThe impacts of intravenous (i.v.) and i.t. injections of ^99mTc-MPDME and ^99mTc-MPDS on biodistribution were studied. The developed MPDME showed spherical droplets with mean PS (74.00 ± 5.69 nm), PDI (0.25 ± 0.03), and ZP (33.90 ± 0.90 mV). Labeling yield of ^99mTc-MPDME and ^99mTc-MPDS was 97.00% ± 0.60% and 92.02% ± 0.45%, respectively. MPD and ^99mTc-MPD showed almost same binding affinity with DNA binding site. Biodistribution results showed that i.t. injection of ^99mTc-MPDME significantly enhanced tumor retention compared to i.v. route.CONCLUSIONSHerein, the authors concluded that microemulsion could be used as i.t. injectable delivery vehicle to improve targeting and tumor retention of MPD.

2018-07-01·International Journal of Pharmaceutics2区 · 医学

Design and development of microemulsion systems of a new antineoplaston A10 analog for enhanced intravenous antitumor activity: In vitro characterization, molecular docking, 125I-radiolabeling and in vivo biodistribution studies

2区 · 医学

Article

作者: El-Kolaly, Mohamed T ; Abdelbary, Aly A ; Tadros, Mina I ; Ibrahim, Ismail T ; Aboumanei, Mohamed H

A10, (3-phenylacetylamino-2,6-piperidinedione), is a natural peptide with broad antineoplastic activity. Recently, in vitro antitumor effect of a new A10 analog [3-(4-methoxybenzoylamino)-2,6-piperidinedione] (MPD) has been verified. However, poor aqueous solubility represents an obstacle towards intravenous formulation of MPD and impedes successful in vivo antitumor activity. To surmount such limitation, MPD microemulsion (MPDME) was developed. A 3¹2² full factorial design using Design-Expert® software was adopted to study the influence of different parameters and select the optimum formulation (MPDME1). Transmission electron microscopy (TEM) displayed spherical droplets of MPDME1. The cytotoxicity of MPDME1 in Michigan Cancer Foundation 7 (MCF-7) breast cancer cell line exceeded that of MPD solution (MPDS) and tamoxifen. Compatibility with injectable diluents, in vitro hemolytic studies and in vivo histopathological examination confirmed the safety of parenteral application of MPDME1. Molecular docking results showed almost same binding affinity of A10, MPD and ¹²⁵I-MPD with histone deacetylase 8 (HDAC8) receptor. Accordingly, radioiodination of MPDME1 and MPDS was done via direct electrophilic substitution reaction. Biodistribution of ¹²⁵I-MPDME1 and ¹²⁵I-MPDS in normal and tumor (ascites and solid) bearing mice showed high accumulation of ¹²⁵I-MPDME1 in tumor tissues. Overall, the results proved that MPDME represents promising parenteral delivery system capable of improving antineoplastic activity of MPD.

100 项与 Antineoplaston A10 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11702

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
脑干胶质瘤	临床3期	-	Burzynski Research Institute, Inc.	2025-06-01
卵巢上皮癌	临床3期	美国	Burzynski Research Institute, Inc.	1996-03-05
前列腺腺癌	临床3期	美国	Burzynski Research Institute, Inc.	1996-02-27
转移性前列腺癌	临床3期	美国	Burzynski Research Institute, Inc.	1996-02-27
中枢神经系统横纹肌瘤	临床3期	美国	Burzynski Research Institute, Inc.	1996-02-01
高级别胶质瘤	临床3期	美国	Burzynski Research Institute, Inc.	1994-04-01
复发性恶性胶质瘤	临床3期	美国	Burzynski Research Institute, Inc.	1994-04-01
原发性恶性肝肿瘤	临床3期	美国	Burzynski Research Institute, Inc.	1977-03-21
室管膜瘤	临床3期	美国	Burzynski Research Institute, Inc.	1966-07-01
低级别 B 细胞非霍奇金淋巴瘤	药物发现	美国	Burzynski Research Institute, Inc.	1996-03-06

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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


NCT00003487 (CTgov)	临床2期	食管腺癌	8	Atengenal+Astugenal	廠簾鹽觸壓糧鏇製憲艱(築廠夢艱壓鹽積糧觸鬱) = 齋構鏇遞糧壓壓網繭憲鹹鹹夢壓顧壓鬱醖鏇築 (顧蓋顧衊糧襯選糧獵襯, 膚鏇鏇積鬱襯選簾淵獵 ~ 鹽觸膚簾顧廠鹹襯鬱膚) 更多	-	2021-05-14
NCT00003508 (CTgov)	临床2期	恶性间皮瘤	8	Atengenal+Astugenal	(壓糧製鬱憲製簾築膚製) = 積鹹憲夢繭鹽淵製顧夢憲顧醖餘製簾選膚範鏇 (積繭糧餘鑰鹹獵範鏇觸, 餘鬱鏇淵製製範獵繭醖 ~ 壓鹽鏇鏇繭醖艱襯糧鹹) 更多	-	2021-02-21
NCT00003511 (CTgov)	临床2期	多发性骨髓瘤	5	Atengenal+Astugenal	(襯獵艱淵鬱範夢繭夢鏇) = 淵夢網糧構鑰繭衊鑰窪觸築顧襯艱範選齋膚網 (築糧構簾壓製淵壓積繭, 艱窪窪積選鏇製艱網範 ~ 淵襯積壓簾蓋鬱齋廠網) 更多	-	2021-01-28
NCT00003509 (CTgov)	临床2期	黑色素瘤	13	Atengenal+Astugenal	(夢醖壓選獵襯積獵製鏇) = 壓蓋鑰窪獵獵憲蓋憲積襯鹽遞膚積鹽簾獵簾淵 (憲鑰獵積積觸網遞鹹夢, 鹽衊鬱齋餘鹽淵鏇觸淵 ~ 膚積簾繭獵網鏇顧積簾) 更多	-	2020-12-19
NCT00003498 (CTgov)	临床2期	非霍奇金淋巴瘤	5	Atengenal+Astugenal	(蓋簾醖蓋簾糧襯鑰衊憲) = 願網艱築願築艱艱鑰繭夢積觸壓鹹窪遞膚鑰鹹 (鏇糧膚夢鬱鑰鬱構獵鬱, 願觸網積鬱膚繭餘願鬱 ~ 夢鏇繭選鑰膚範網餘獵) 更多	-	2020-12-19
NCT00003531 (CTgov)	临床2期	胰腺腺癌	15	Atengenal+Astugenal	(鹹鑰繭廠鏇鹹襯蓋鑰願) = 壓夢鑰襯蓋鑰遞衊選衊繭構顧獵鑰範壓窪鏇顧 (鹹壓齋壓觸淵遞築鏇齋, 襯壓淵夢範憲憲鏇網鏇 ~ 膚構淵鹽壓齋構襯遞鏇) 更多	-	2020-12-17
NCT00003526 (CTgov)	临床2期	腺癌 \| 原发部位不明恶性肿瘤	8	Atengenal+Astugenal	(鹹夢鑰遞顧膚鬱築範鑰) = 選願繭艱鬱選糧壓蓋鹹積網願鬱鑰夢製鬱構糧 (鑰襯遞簾觸獵醖繭淵觸, 壓構網壓廠製範齋鏇窪 ~ 醖選築壓齋蓋齋淵廠獵) 更多	-	2020-12-17
NCT00003492 (CTgov)	临床2期	未分化大细胞肺癌	9	Atengenal+Astugenal	鬱鹽網觸窪製鑰範觸鏇(鹽艱鹹築獵鹹願範糧鏇) = 鹹壓蓋網願糧願範淵鹹網糧壓廠製艱築憲襯選 (獵夢壓蓋簾醖選醖鬱鑰, 製夢醖鏇襯鏇願網齋鹽 ~ 範夢製鏇築淵觸鏇顧膚) 更多	-	2020-12-16
NCT00003499 (CTgov)	临床2期	低级别 B 细胞非霍奇金淋巴瘤	31	Atengenal+Astugenal	(簾鏇繭網糧獵襯淵築艱) = 鏇鬱餘積構鬱憲壓廠鹽築膚淵窪蓋獵艱壓鬱鏇 (顧壓鏇鑰餘醖夢膚簾蓋, 廠遞簾遞廠淵獵夢蓋淵 ~ 糧廠衊襯鹹獵廠艱構鑰) 更多	-	2019-04-16
NCT00003453 (CTgov)	临床2期	肾上腺皮质癌	6	Atengenal+Astugenal	(範鑰顧鏇膚積蓋醖鑰艱) = 鹽繭糧築製製範鑰窪鹹壓壓選鹽齋膚窪壓積鹹 (蓋糧壓構繭顧鑰築艱範, 淵繭夢獵遞襯憲簾鹹齋 ~ 壓蓋選衊壓網製網醖廠) 更多	-	2018-05-09