Delving into the Latest Updates on BAY-876 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BAY 876, BAY876

Target

GLUT1

Action

inhibitors

Mechanism

GLUT1 inhibitors(Glucose transporter 1 inhibitors)

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

Neoplasms

Originator Organization

Bayer AG

Active Organization-

Inactive Organization

Bayer AG

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC24H16F4N6O2

InChIKeyBKLJDIJJOOQUFG-UHFFFAOYSA-N

CAS Registry1799753-84-6

Disulfidptosis, a novel form of programmed cell death characterized by cystine accumulation and disulfide stress, primarily affects metabolically active tumors like bladder cancer, which is often considered to be a highly metabolic and energy-consuming tumor. However, translating disulfidptosis induction into clinical practice face substantial obstacles, including the limited solubility of key inducers, insufficient cystine buildup within cells, and cellular mechanisms regulating the NADP⁺/NADPH equilibrium. To fully unlock the therapeutic potential of disulfidptosis, a promising solution has emerged in the form of nanotechnology combined with sonodynamic therapy (SDT). This study reports a novel approach that enhances disulfidptosis through SDT, simultaneously promoting immunogenic cell death (ICD) and improving the immunosuppressive tumor microenvironment. The system, SPCP/CCP@Bay, comprises a degradable sonodynamic-pseudo-conjugate-polymer (SPCP) and a cystine-containing polymer (CCP), loaded with Bay-876. Following intravenous administration, SPCP/CCP@Bay effectively accumulates at tumor sites. Under ultrasound radiation, SPCP/CCP@Bay effectively releases Bay-876, disrupts the intracellular redox balance, releases cystine from CCP, and induces disulfidptosis. Moreover, SPCP/CCP@Bay induces ICD and synergizes with PD-1 monoclonal antibodies (α-PD-1) to suppress tumor growth. This integrated strategy holds significant promise in reshaping the tumor microenvironment, converting "cold tumors" to "hot tumors", and advancing the field of cancer immunotherapy.

01 May 2025·FREE RADICAL BIOLOGY AND MEDICINE

Glucose protects cultured retinal cells from oxidative injury via the pentose phosphate pathway

Article

Author: Casson, Robert J ; Wood, John P M ; Chidlow, Glyn

PURPOSE:

Oxidative injury has been implicated in a range of common retinal neurodegenerative disorders. Protecting the retina from such an insult could therefore prove clinically beneficial. We sought to investigate whether glucose, acting via the pentose phosphate pathway (PPP), was able to counteract oxidative cytotoxicity to retinal cells in culture.

EXPERIMENTAL:

Mixed retinal neuron-glial cultures were prepared from Sprague-Dawley rat neonates and used at 7 days in vitro; neuron-only and Müller glial cell-only mono-cultures were subsequently prepared from these cultures. At appropriate stages, cultures were treated with t-butyl hydroperoxide (tbH; 10 nM-1 mM) in glucose/pyruvate-free DMEM to induce oxidative stress. Some cultures were co-treated with glucose. Additional compounds were co-applied to inhibit glycolysis, PPP, cystine uptake, glutathione biosynthesis and glutathione reductase (GR). The effect of glucose on stimulation of reactive oxygen species (ROS), as well as levels of glutathione and NADPH were also investigated.

RESULTS:

Oxidative stress resulted in cytotoxicity to both retinal neurons and glial cells. Glucose was able to abrogate the toxicity to glial cells in mono-cultures and mixed cultures, but could only provide protection to neurons in the mixed cultures when glial cells were also present. Glucose was additionally shown to prevent stimulation of ROS and oxidative stress-induced depletions of glutathione and NADPH. Inhibition of PPP, cystine uptake or GR all diminished the protective response of glucose.

CONCLUSION:

Glucose prevented oxidative stress to retinal cells via the PPP. Neurons were not subjected to glucose-induced protection except when glial cells were present, implying the passage of a transmissible mediator or other protective action between the two cell types.

01 Mar 2025·Journal of Advanced Research

Exploiting metabolic vulnerabilities through synergistic ferroptosis and disulfidptosis for breast cancer therapy

Article

Author: Xu, Ziting ; Gao, Mengdan ; Li, Yingjia ; Lan, Haibo ; Zhang, Li ; Liang, Yu ; Liu, Minyi ; Li, Qiuyu ; Zhao, Bingxia ; Gao, Yang

INTRODUCTION:

Ferroptosis represents a promising therapeutic approach for breast cancer treatment. However, cancer cells can develop resistance through the SLC7A11-GSH-GPX4 axis, wherein increased SLC7A11 expression enhances cystine uptake, replenishes GSH, and reactivates GPX4. Notably, cells with high SLC7A11 expression become vulnerable to disulfidptosis under glucose-deprived conditions.

OBJECTIVES:

We aimed to develop a dual-mode therapeutic strategy that simultaneously induces ferroptosis and disulfidptosis by targeting both lipid peroxidation and glucose metabolism in breast cancer cells.

METHODS:

Fe-Cu-SS metal-organic frameworks (MOFs) loaded with BAY876 (FCSP@876 MOFs) were synthesized to enhance ferroptosis and trigger disulfidptosis in breast cancer cells. The MOFs were characterized using transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and UV-Vis spectroscopy. In vitro experiments demonstrated that FCSP@876 MOFs increased reactive oxygen species (ROS) levels and lipid peroxidation while depleting NADPH. Western blotting and actin filament staining confirmed the underlying mechanisms. In vivo xenograft experiments in BALB/c mice assessed the synergistic effects of ferroptosis and disulfidptosis induction.

RESULTS:

During ferroptosis induction, cancer cells exhibited an adaptive upregulation of SLC7A11 expression. FCSP@876 MOFs effectively counteracted this resistance mechanism by simultaneously inducing ferroptosis and restricting glucose uptake through BAY876, leading to NADPH depletion and subsequent disulfidptosis. Both in vitro and in vivo experiments demonstrated the enhanced therapeutic efficacy of this dual-mode strategy compared with single-mode treatments.

CONCLUSION:

This study successfully developed a novel therapeutic strategy that combines ferroptosis and disulfidptosis using FCSP@876 MOFs, offering a promising approach for overcoming ferroptosis resistance in breast cancer therapy.

100 Deals associated with BAY-876

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