Delving into the Latest Updates on Antineoplaston A10 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Antineoplaston A 10, Atengenal

+ [1]

Target-

Mechanism

Apoptosis inducers

Therapeutic Areas

NeoplasmsImmune System DiseasesInfectious Diseases+ [9]

Active Indication-

Inactive Indication

Adenocarcinoma of EsophagusAdenocarcinoma of LungAdenocarcinoma of prostate+ [39]

Originator Organization

Burzynski Research Institute, Inc.

Active Organization-

Inactive Organization

Burzynski Research Institute, Inc.

Drug Highest PhaseSuspendedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC13H14N2O3

InChIKeyOQGRFQCUGLKSAV-JTQLQIEISA-N

CAS Registry91531-30-5

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).

Start Date01 Jun 2027

Sponsor / Collaborator

Burzynski Research Institute, Inc.

NCT02887040 / Not yet recruitingPhase 3IIT

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.

Start Date01 Jun 2025

Sponsor / Collaborator

Burzynski Research Institute, Inc.

KCT0008386 / Active, not recruitingPhase 3

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)

Start Date31 Aug 2022

Sponsor / Collaborator

Huons Meditech Co., Ltd.

100 Clinical Results associated with Antineoplaston A10

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100 Translational Medicine associated with Antineoplaston A10

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100 Patents (Medical) associated with Antineoplaston A10

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48

Literatures (Medical) associated with Antineoplaston A10

03 May 2024·Toxicology Mechanisms and Methods

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

Article

Author: 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.

01 Aug 2018·Cancer Biotherapy and RadiopharmaceuticalsQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: 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.

01 Jul 2018·International Journal of PharmaceuticsQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: 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 Deals associated with Antineoplaston A10

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11702

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Low Grade B-Cell Non-Hodgkin's Lymphoma	Phase 2	US	Burzynski Research Institute, Inc.	06 Mar 1996
Ovarian Epithelial Carcinoma	Phase 2	US	Burzynski Research Institute, Inc.	05 Mar 1996
Brain Stem Glioma	Phase 2	US	Burzynski Research Institute, Inc.	01 Mar 1996
Adenocarcinoma of prostate	Phase 2	US	Burzynski Research Institute, Inc.	27 Feb 1996
Metastatic Prostate Carcinoma	Phase 2	US	Burzynski Research Institute, Inc.	27 Feb 1996
Rhabdoid Tumor of the CNS	Phase 2	US	Burzynski Research Institute, Inc.	01 Feb 1996
High grade glioma	Phase 2	US	Burzynski Research Institute, Inc.	01 Apr 1994
Recurrent Malignant Glioma	Phase 2	US	Burzynski Research Institute, Inc.	01 Apr 1994
Primary Malignant Liver Neoplasm	Phase 2	US	Burzynski Research Institute, Inc.	21 Mar 1977
Ependymoma	Phase 2	US	Burzynski Research Institute, Inc.	01 Jul 1966

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00003487 (CTgov)	Phase 2	Adenocarcinoma of Esophagus	8	Atengenal+Astugenal	gyyugbrprv(hmwbdkdjmk) = kehwjrjuwj jhrbhzazna (owaelmexyd, izytkawtwy - ronewxnwyl) View more	-	14 May 2021
NCT00003508 (CTgov)	Phase 2	Mesothelioma, Malignant	8	Atengenal+Astugenal	oxevfffugy(lfjkrfxbpf) = veamfgtsto ftwmsnwugc (oyjtxwdeoo, qsfffzcstf - blmoagumob) View more	-	21 Feb 2021
NCT00003511 (CTgov)	Phase 2	Multiple Myeloma	5	Atengenal+Astugenal	kjgpxiyuan(mbnjyyucie) = hohvwexxvj ihtpyageii (qggtanokqo, shmwwsrdze - skpoyarter) View more	-	28 Jan 2021
NCT00003498 (CTgov)	Phase 2	Non-Hodgkin Lymphoma	5	Atengenal+Astugenal	ulxpbsujet(yqslhjtbki) = rcflrhajcz ugogzlppob (kdwanfpxkh, ivkldbjtqr - xcknafrwww) View more	-	19 Dec 2020
NCT00003509 (CTgov)	Phase 2	Melanoma	13	Atengenal+Astugenal	(fycklfyado) = iokpzsniev oadweizgsm (vlqhbvjpbe, mvoyttoqkf - kuxllbimrx) View more	-	19 Dec 2020
NCT00003526 (CTgov)	Phase 2	Adenocarcinoma \| Unknown Primary Neoplasms	8	Atengenal+Astugenal	(ohdujpmmsr) = guvumxdkro mplrmwhdva (jznnchmhfk, jxwxxxgeti - lpyobpntng) View more	-	17 Dec 2020
NCT00003531 (CTgov)	Phase 2	Pancreatic adenocarcinoma	15	Atengenal+Astugenal	ysjlrflpup(qhjmcrhfzx) = fndaqlinii bbnhnyjxdw (pihafqxagb, coykfdtifh - eoeftndsyp) View more	-	17 Dec 2020
NCT00003492 (CTgov)	Phase 2	undifferentiated large cell lung cancer	9	Atengenal+Astugenal	xoujiapypv(ejewxqrexr) = ehbpuukqdh ydhrikrvon (upbfymvqfc, rbwchppdgn - livfxjmlur) View more	-	16 Dec 2020
NCT00003499 (CTgov)	Phase 2	Low Grade B-Cell Non-Hodgkin's Lymphoma	31	Atengenal+Astugenal	(okmnkrztzs) = kxnptimzqp bxaxgbsgcm (gzlrolfepd, mficsdrwcz - izgyqyelms) View more	-	16 Apr 2019
NCT00003453 (CTgov)	Phase 2	Adrenocortical Carcinoma	6	Atengenal+Astugenal	(epibpbmahh) = nltxsukwon ipakurtsnz (upobfajetu, iivdpdlcwh - iqtzmlaqag) View more	-	09 May 2018