Targeting Metabolic and pH Regulatory Pathways in Cancer via Dual Inhibition of Nicotinamide Phosphoribosyltransferase and Carbonic Anhydrases IX and XII We report the first dual inhibitors of the tumor-associated carbonic anhydrases (hCA IX and XII) and nicotinamide phosphoribosyltransferase (NAMPT), designed to target metabolic and pH-regulatory mechanisms critical for tumor growth and resistance. Enzymatic assays identified hits showing potent nanomolar inhibition of both targets and superior efficacy compared to reference inhibitors. Computational studies elucidated key ligand–target interactions and structure–activity relationship. In high-throughput screening cellular assays, several compounds outperformed monotherapies with strong antiproliferative effects against renal carcinoma, glioblastoma, and colorectal cancer cells under normoxic and hypoxic conditions, and limited toxicity toward nonmalignant cells. In three-dimensional (3D) spheroids, compound 45 reduced the cumulative spheroid area approximately 10-fold more than the single-target inhibitors FK866 or SLC-0111 and induced apoptosis through NAD depletion, mitochondrial dysfunction, and suppression of ERK/mTOR signaling. These results support dual hCA IX/XII–NAMPT inhibition as an effective strategy to impair tumor growth and survival under hypoxic stress.

New J Med Chem: first dual inhibitors of NAMPT and CA IX/XII (hypoxia-linked pH control). In 3D spheroids, compound 45 reduced cumulative spheroid area ~10× vs single-target controls.

#HypoxyLab enabled controlled hypoxia (1% O2) + #GelCount 2 enabled automated sizing.

#CancerResearch #Hypoxia

In Vitro Dissolved Oxygen Monitoring in Hypoxia Chambers Explore how an in vitro system that can be utilized within hypoxic chambers ensures precise dissolved oxygen control in cell cultures and media. Hypoxia chambers are used worldwide by research investi...

Stop guessing pericellular oxygen and just measure it.

Guide to dissolved O2 in hypoxia chambers: think in mmHg, verify in media pO2, track stability with #OxyLite and #HypoxyLab.

Read here: www.oxford-optronix.com/resources/in...

#pO2 #Hypoxia #ResearchTools

What if oxygen is the switch for FLASH at the molecular scale?
At 5% O₂, UHDR yields fewer DNA strand breaks than LDR & at ~21% O₂ that advantage vanishes. #HypoxyLab set ~40 mmHg O₂ and #OxyLite confirmed O₂ and sealing to keep conditions true.

Read here👉 arxiv.org/pdf/2510.15478

Not All Tumors Are Alike: Varying Efficacy of FLASH Across Tumor Types and Oxygenation Status in Spheroid Models - PubMed This preclinical study suggests that tumor iso-efficacy with UHDR may not hold true for all cancer types and is associated with oxygen level.

What if FLASH response is tuned by oxygen and spheroid size?

In 3D models, UHDR matched conventional dose rates in ambient oxygen for small spheroids, but hypoxia increased the dose needed for control by about 7 to 14 percent.

#HypoxyLab maintained 8 mmHg O2 to model hypoxia.

#FLASH #Hypoxia

Intra-tumoral hypoxia promotes CD8+ T cell dysfunction via chronic activation of integrated stress response transcription factor ATF4 Metabolic stress imposed by the tumor microenvironment (TME) promotes T cell dysfunction and limits antitumor immunity. Alicea Pauneto et al. demonstrate the hypoxia within the TME drives chronic acti...

What if tumor hypoxia is the switch for CD8⁺ T-cell exhaustion?

New Immunity paper shows chronic hypoxia drives ATF4 leading to mitochondrial stress & death. ISRIB restores T-cell fitness and PD-1 response.

The #HypoxyLab was set to 1.5% O₂ for 96 h to model cell stress.

#Hypoxia #Immunotherapy

Just dropped: a 2-min explainer on the #HypoxyLab — a sealed, mmHg-controlled hypoxia chamber used in cancer, stem cell, and neuroscience research. Come see our novel approach to an oxygen controlled workstation!

and yes, there’s a blooper at the end 👀

#hypoxia #researchtools #science #labtech

An episodic burst of massive genomic rearrangements and the origin of non-marine annelids - Nature Ecology & Evolution An analysis of annelid genomes reveals massive reshuffling of chromosomes in the ancestral lineage leading to clitellates, a clade composed of non-marine annelids, with potential implications for the ...

How to evolve from ocean to soil? A genome explosion!
New Nature study reveals clitellates underwent massive chromosomal scrambling—shattering ancestral gene order.
The #HypoxyLab was key: its precise O₂ control validated #adaptive responses.
#Evolution #Ecology

🔗: www.nature.com/articles/s41...

Hypoxia-inducible factor 1α modulates acrolein-induced cellular damage in bronchial epithelial cells Acrolein, a highly reactive α,β-unsaturated aldehyde, is a widespread environmental pollutant. It is generated during the incomplete combustion of mat…

HIF-1α’s dual role in acrolein lung damage revealed by a @baylor.bsky.social team!
Study shows hypoxia via #HypoxyLab lets HIF-1α either worsen or protect cells, depending on exposure. Key for understanding smoke/pollution toxicity! #Hypoxia #LungHealth

www.sciencedirect.com/science/arti...

Contamination Control in Hypoxia Chambers Effective contamination control in hypoxia chambers is essential for reliable research. The HypoxyLab features a self-contained and sealed chamber that creates a stable low-oxygen environment while pr...

Sterility in hypoxia chambers is vital for reliable cell culture. Our whitepaper outlines strategies to combat contamination and shows how the innovative #HypoxyLab system—with HEPA filtration, UV sterilization & a smart letterbox—protects your experiments.

#CellCulture #LabSafety #Innovation