Delving into the Latest Updates on Alpha-Tocopheryloxyacetic acid with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

α-TEA

Target-

Action

stimulants

Mechanism

Apoptosis stimulants, Immunostimulants

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

LymphomaSarcomaUterine Cervical Cancer

Inactive Indication

Hormone refractory breast cancerMetastatic human epidermal growth factor 2 positive carcinoma of breast

Originator Organization

Veana Therapeutics, Inc.

Active Organization

Veana Therapeutics, Inc.

Inactive Organization

Veana Therapeutics LLC

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC31H52O4

InChIKeyLCFWOFKPFDWYLR-CEFNRUSXSA-N

CAS Registry261929-52-6

This phase I trial studies the side effects and best dose of alpha-TEA when given together with trastuzumab and to see how well they work for the treatment of HER2+ breast cancer that does not respond to treatment (refractory) and has spread to other places in the body (metastatic). Anti-cancer treatment, such as alpha-TEA, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Alpha-TEA may also alter cancer growth by stimulating the body's immune response against the tumor. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Giving alpha-TEA and trastuzumab may work better for the treatment of HER2+ refractory and metastatic breast cancer compared to usual treatment.

Start Date08 Apr 2020

Sponsor / Collaborator

Veana Therapeutics LLC

[+1]

NCT02192346

/ CompletedPhase 1IIT

Phase I Study of Alpha-tocopheryloxyacetic Acid (α-TEA) in Patients With Advanced Cancer

The goal of this study is to find the highest dose of α-TEA that can be given to patients safely, to identify potential side effects of α-TEA, and to measure the amount of α-TEA in patients' blood.
Additional goals of this study are to monitor the effect on tumors, to check for specific immune cells circulating in the blood, and to see if there are certain features of tumors that make it possible to predict the response to α-TEA.

Start Date04 Aug 2014

Sponsor / Collaborator

Providence Health & Services

100 Clinical Results associated with Alpha-Tocopheryloxyacetic acid

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100 Translational Medicine associated with Alpha-Tocopheryloxyacetic acid

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100 Patents (Medical) associated with Alpha-Tocopheryloxyacetic acid

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74

Literatures (Medical) associated with Alpha-Tocopheryloxyacetic acid

01 Dec 2022·Acta Parasitologica

Effect of α-Tocopheryloxy Acetic Acid on the Infection of Mice with Plasmodium berghei ANKA In Vivo and Humans with P. falciparum In Vitro

Article

Author: Umemiya-Shirafuji, Rika ; Kume, Aiko ; Kasai, Shunji ; Nishikawa, Yoshifumi ; Taniguchi, Tomoyo ; Suzuki, Hiroshi ; Ariefta, Nanang R

PURPOSEMalarial parasites are susceptible to oxidative stress. The effects of α-tocopheryloxy acetic acid (α-TEA), a vitamin E analog, on infection by Plasmodium berghei ANKA and P. falciparum in mice and human red blood cells (RBCs), respectively, were examined in this study.METHODSFor in vivo studies in mice, RBCs infected with P. berghei ANKA were inoculated via intraperitoneal injection and α-TEA was administered to C57BL/6 J male mice after infection. The blood-brain barrier (BBB) permeability was examined by Evans blue staining in experimental cerebral malaria at 7 days after infection. The in vitro inhibitory effect of α-TEA on P. falciparum 3D7 (chloroquine-sensitive strain) and K1 (multidrug-resistant strain) was tested using a SYBR Green I-based assay.RESULTSWhen 1.5% α-TEA was administered for 14 days after infection, 88% of P. berghei ANKA-infected mice survived during the experimental period. Nevertheless, all the control mice died within 12 days of infection. Furthermore, the Evans blue intensity in α-TEA-treated mice brains was less than that in untreated mice, indicating that α-TEA might inhibit the destruction of the BBB and progression of cerebral malaria. The in vitro experiment revealed that α-TEA inhibited the proliferation of both the 3D7 and K1 strains.CONCLUSIONThis study showed that α-TEA is effective against murine and human malaria in vivo and in vitro, respectively. Although α-TEA alone has a sufficient antimalarial effect, future research could focus on the structure-activity relationship to achieve better pharmacokinetics and decrease the cytotoxicity and/or the combined effect of α-TEA with existing drugs. In addition, the prophylactic antimalarial activity of premedication with α-TEA may also be an interesting perspective in the future.

01 May 2022·Current Medicinal ChemistryQ2 · MEDICINE

Celecoxib and Dimethylcelecoxib Block Oxidative Phosphorylation, Epithelial-Mesenchymal Transition and Invasiveness in Breast Cancer Stem Cells

Q2 · MEDICINE

Article

Author: García-Amezcua, Marco Antonio ; Gallardo-Pérez, Juan Carlos ; Vargas-Navarro, Jorge Luis ; Belmont-Díaz, Javier Alejandro ; de Guevara, Alhelí Adán-Ladrón ; Rodríguez-Enríquez, Sara ; Robledo-Cadena, Diana Xochiquetzal ; Moreno-Sánchez, Rafael ; Pacheco-Velázquez, Silvia Cecilia

Background:The major hurdles for successful cancer treatment are drug resistance and invasiveness developed by breast cancer stem cells (BCSC).Objective:As these two processes are highly energy-dependent, the identification of the main ATP supplier required for stem cell viability may result advantageous in the design of new therapeutic strategies to deter malignant carcinomas.Methods:The energy metabolism (glycolysis and oxidative phosphorylation, OxPhos) was systematically analyzed by assessing relevant protein contents, enzyme activities, and pathway fluxes in BCSC. Once identified as the main ATP supplier, selective energy inhibitors and canonical breast cancer drugs were used to block stem cell viability and metastatic properties.Results:OxPhos and glycolytic protein contents, as well as HK and LDH activities were several times higher in BCSC than in their parental line, MCF-7 cells. However, CS, GDH, COX activities, and both energy metabolism pathway fluxes were significantly lower (38-86%) in BCSC than in MCF-7 cells. OxPhos was the main ATP provider (>85%) in BCSC. Accordingly, oligomycin (a specific and potent canonical OxPhos inhibitor) and other non-canonical drugs with inhibitory effect on OxPhos (celecoxib, dimethylcelecoxib) significantly decreased BCSC viability, levels of epithelial-mesenchymal transition proteins, invasiveness, and induced ROS over-production, with IC50 values ranging from 1 to 20 μM in 24 h treatment. In contrast, glycolytic inhibitors (gossypol, iodoacetic acid, 3-bromopyruvate, 2-deoxyglucose) and canonical chemotherapeutic drugs (paclitaxel, doxorubicin, cisplatin) were much less effective against BCSC viability (IC50> 100 μM).Conclusion:These results indicated that the use of some NSAIDs may be a promising alternative therapeutic strategy to target BCSC.

01 Jan 2022·GeneQ3 · BIOLOGY

How vitamin E and its derivatives regulate tumour cells via the MAPK signalling pathway?'

Q3 · BIOLOGY

Review

Author: Wang, Lan-Min ; Yu, Zhen-Qi ; Yang, Wan-Xi

In tumour cells, vitamin E and its derivatives play a critical role in the regulation of multiple signalling pathways through their oxidative and nonoxidative functions. To date, there are 8 known natural vitamin E forms and many kinds of derivatives, among which VES and α-TEA have excellent anticancer activities. The MAPK pathway consists of a complex cascade of proteins that control the proliferation, differentiation and apoptosis of tumour cells. The MAPK pathway includes four subfamilies, ERK1/2, JNK1/2, p38 MAPK, and ERK5. Most of the proteins in these subfamilies interact with each other in a complex manner. The anticancer function of vitamin E and its derivatives is closely related to the MAPK cascade. Studies have shown that in tumour cells, α-T/γ-T/γ-T3/δ-T3/VES/α-TEA regulated ERK1/2, prevent tumorigenesis, inhibit tumour cell growth and metastasis and induce cell differentiation, apoptosis, and cell cycle arrest; γ-T3/δ-T3/VES/α-TEA regulates JNK1/2, induce apoptosis, reduce ceramide synthesis and inhibit proliferation; and γ-T3/δ-T3/VES regulate p38 MAPK and induce apoptosis. This paper reviews the role of vitamin E and its derivatives in the MAPK cascade, and tumour cells are used as a model in an attempt to explore the mechanism of their interactions.

100 Deals associated with Alpha-Tocopheryloxyacetic acid

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hormone refractory breast cancer	Phase 1	United States	Veana Therapeutics LLC	08 Apr 2020
Metastatic human epidermal growth factor 2 positive carcinoma of breast	Phase 1	United States	Veana Therapeutics LLC	08 Apr 2020
Lymphoma	Phase 1	-	Veana Therapeutics, Inc.	-
Sarcoma	Phase 1	-	Veana Therapeutics, Inc.	-
Uterine Cervical Cancer	Phase 1	-	Veana Therapeutics, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02192346 (P8, SITC2016)	Phase 1	Advanced cancer	12	Alpha-tocopheryloxyacetic acid (Î±-TEA) 2.4 mg/kg	ruebvztkak(akswzwmhyi) = 6 developed atrial fibrillation (AF) after starting Î±-TEA vplxyujqzd (tnunmnwccv ) View more	Positive	08 Dec 2016
				Alpha-tocopheryloxyacetic acid (Î±-TEA) 4.8 mg/kg