Delving into the Latest Updates on NSC4056 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Aurintricarboxylic acid, NSC4056

Target

CGL

Action

inhibitors

Mechanism

CGL inhibitors(cystathionine gamma-lyase inhibitors)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Hypotension

Inactive Indication-

Originator Organization

Shanghai Jiao Tong University

Active Organization

Shanghai Jiao Tong University

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC22H14O9

InChIKeyGIXWDMTZECRIJT-UHFFFAOYSA-N

CAS Registry4431-00-9

Currently, a robust process using healthy Chinese hamster ovary (CHO) cells, the dominating host for biopharmaceutical protein therapeutics, is crucial for high productivity and successful scaling-up. However, issues which are originated from cell performance and detrimental to protein products such as dramatic viability drop and accumulation of toxic metabolites still exist. Aurintricarboxylic acid (ATA), reported as an antioxidant chelator to prevent apoptosis and boost cell growth, was applied as an additive in this study to address the above problems.

METHODS:

Two CHO cells were cultivated by fed-batch culture with ATA of different concentrations and adding strategies supplemented. The reactive oxygen species (ROS) test and confocal microscopy have been used to illustrate the working mechanism of ATA.

RESULTS:

ATA was proved to be effective in maintaining viability and improving lactate performance in the late fed-batch culture stage for both tested clones. Briefly, the harvest viability was increased by at least 10% after ATA was introduced, and the suppression of lactate accumulation was observed with ATA addition. Moreover, besides adding ATA in the fed-batch stage, a novel and favorable process to involve ATA in seed train was developed, which improved the performance of seed and further benefitted the cell performance and productivity during fed-batch culture. And the ATA was detected to penetrate into CHO cells and suppress the ROS generation intracellularly.

CONCLUSION:

Overall, this study advances current knowledge with respect to ATA's capability of enhancing cell performances for CHO cell manufacturing and introduces a novel process of hyper seed train.

10 Jun 2025·ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

ATP‐Assisted Electron and Proton Transfer Boosting Redox Metabolism‐Induced Ferroptosis and Apoptosis for Cancer Therapy

Article

Author: An, Shangjie ; Jia, Xiaodan ; Jiang, Xiue ; Wang, Yue ; Zhen, Wenyao

Abstract:

Compared to the intractability of traditional apoptosis, the vulnerability exposed by cancer cell metabolic reprogramming provides an advantage for ferroptosis treatment. Herein, we developed vanadate and aurintricarboxylic acid coordination nanoparticles (VAP NPs) that synergistically trigger dual cell death pathways. This nanoplatform leveraged dual‐Russell mechanisms and Fenton reactions to generate singlet oxygen/hydroxyl radicals in the tumor microenvironment (TME) while depleting glutathione via vanadium redox cycling, thereby silencing glutathione peroxidase 4 and modulating the Kelch‐like ECH‐associated protein 1 (KEAP1)/nuclear factor erythroid 2‐related factor 2 (NRF2)/heme oxygenase 1 (HMOX1) axis. Notably, TME‐overexpressed adenosine triphosphate (ATP) acted as a biochemical catalyst, accelerating the transfer of protons and electrons during reactive oxygen species generation to amplify therapeutic efficacy. Therefore, VAP NPs could achieve outstanding efficacy for intrinsically stimulated synergy of ferroptosis and apoptosis in tumor therapy. This study provides reference for revealing the new function of ATP in enhancing the regulation of redox metabolism.

01 Jun 2025·British Journal of Pharmacology

Chemosensory signalling in human sperm is controlled by Ca²⁺ influx via CatSper and Ca²⁺ clearance via plasma membrane Ca²⁺ ATPases

Article

Author: Fußhöller, David ; Strünker, Timo ; Kaupp, U. Benjamin ; Münchow, Jens ; Temme, Louisa ; Brenker, Christoph ; Bojovic, Vesna ; Herrmann, Leonie ; Trugge, Carla ; Zhu, W. Felix ; Jikeli, Jan ; Mittermair, Teresa

Abstract:

Background and Purpose:

Loss of function of the sperm‐specific Ca2+ channel CatSper is a common channelopathy that causes male infertility. CatSper controls the intracellular Ca2+ concentration and, thereby, the motility of human sperm. Activation of CatSper by oviductal ligands evokes a transient Ca2+ increase, which entails changes in the flagellar beat that are required for fertilisation. The CatSper‐mediated Ca2+ influx has been studied extensively, whereas the mechanisms underlying Ca2+ clearance and recovery from Ca2+ influx have remained ill‐defined.

Experimental Approach:

We examined how pharmacological suppression of Ca2+ export from the cytosol into the extracellular space or Ca2+ uptake into intracellular stores affects the resting Ca2+ concentration and CatSper‐mediated Ca2+ signals in human sperm. We studied sperm of healthy volunteers and infertile men lacking functional CatSper channels, using kinetic Ca2+‐ and pH‐fluorometry as well as patch‐clamp recordings.

Key Results:

We show that Ca2+ entering human sperm via CatSper is predominantly, if not exclusively, exported by plasma membrane Ca2+ ATPases (PMCAs). Na+/Ca2+ exchange and Ca2+ uptake into intracellular stores or mitochondria play no or only a negligible role in Ca2+ clearance in human sperm.

Conclusions and Implications:

Ca2+ signalling in human sperm is controlled by the functional interplay of CatSper and PMCAs, that is, the balance between Ca2+ influx and Ca2+ export that is required for human sperm function and fertilisation.

100 Deals associated with NSC4056

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