Design, Synthesis, and Characterization of Prodrugs of Sulfonamide TLR4 Signaling Inhibitor TAK-242 (Resatorvid) We have previously reported two prodrug designs for the delivery of the potent TLR4 inhibitor TAK-242. Our initial design was used to covalently link TAK-242 to pancreatic islets using a linker to afford sustained delivery of the active drug after transplant. Those drug-eluting islets provided local inhibition of TLR4-linked inflammation and improved islet graft survival. Here, we describe a third family of TAK-242 prodrugs featuring two rate modulating sites, a self-immolative aniline-stabilized methylene spacer bonded directly to the sulfonamide nitrogen, an alcohol tether for bioconjugation, and a β-eliminative aryl-sulfone “trigger”. These prodrugs rapidly release TAK-242 after activation by β-elimination and a rapid subsequent 1,2-elimination, cleanly releasing the drug without detectable intermediates. This manuscript reports the preparation and characterization of a series of methylene-linked TAK-242 prodrugs, evaluating the impact of various modifications on drug release kinetics.

Design, Synthesis, and Characterization of Prodrugs of Sulfonamide TLR4 Signaling Inhibitor TAK-242 (Resatorvid) pubs.acs.org/doi/10.1021/... @pubs.acs.org

#MedicinalChemistry #DrugDesign #ProdrugStrategy #InflammationResearch #Immunology #Pharmacokinetics #Therapeutics #DrugDevelopment

🧬 SAMHD1 deletion unveils obesity's inflammatory secrets! Metabolic rewiring triggers mitochondrial DNA neosynthesis - a game-changing molecular insight 🔥 #Genomics #InflammationResearch #MetabolicHealth https://emmecola.github.io/genomics-daily

Maternal LPS exposure disrupts offspring gut motility: TLR4–PIEZO1 interaction enhances 5-HT–mediated dysfunction, revealing a novel inflammation-mechanotransduction link.
#GutHealth #TLR4 #PIEZO1 #InflammationResearch #Neurogastroenterology
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New findings show Galectin-3 in tumor-stromal cells boosts gemcitabine resistance in pancreatic adenocarcinoma by suppressing oxidative phosphorylation. A key mechanism in therapy failure.
#PancreaticCancer #Galectin3 #InflammationResearch #CancerBiology
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Paternal psychological strengths linked to lower maternal inflammation in married couples A new study published in Biopsychosocial Science and Medicine suggests that a father’s psychological resilience may play a significant role in the biological health of his pregnant partner and the duration...

Paternal psychological strengths linked to lower maternal inflammation in married couples #Science #HealthandMedicine #MentalHealth #MaternalHealth #PsychologicalStrengths #InflammationResearch

m6A RNA methylation is emerging as a key regulator in autoimmune diseases, shaping immune activation + new therapeutic avenues.
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Researchers find link between psychosocial stress and early signs of heart inflammation in women Understand the critical connection between stress and cardiovascular disease, especially for women, according to recent findings.

Researchers find link between psychosocial stress and early signs of heart inflammation in women.
https://hospitalnews.com/mri-stress/
#PsychosocialStress #HeartHealth #WomenInScience #InflammationResearch #WomenHealth

This Inexpensive Anti-Inflammatory Pill Could Reduce Risk of Heart Attack and Stroke A common gout drug may unexpectedly lower the risk of heart attacks and strokes, according to a major new review A commonly used and affordable medication for gout may help lower the risk of heart attacks...

This Inexpensive Anti-Inflammatory Pill Could Reduce Risk of Heart Attack and Stroke #Science #HealthandMedicine #Cardiology #HealthInnovation #InflammationResearch

Tiny chips hitch a ride on immune cells to sites of inflammation Standard brain implants use electrodes that penetrate the gray matter to stimulate and record the activity of neurons. These typically need to be put in place via a surgical procedure. To go around that...

Tiny chips hitch a ride on immune cells to sites of inflammation #Science #Biology #CellBiology #ImmuneResponse #InflammationResearch #BiomedicalEngineering

Many immune diseases lack effective treatments. In this webinar, learn how how 3D disease models can improve drug discovery for inflammation & IBD and improve pre-clinical predictability for immune-targeting therapies.

Watch now: shorturl.at/BZygd
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Antimicrobial peptides modulate lipopolysaccharide-induced gene expression of cytokines IL1β and IL10 and toll-like receptor 4 in rat blood leukocytes <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d20589725e116"> <b>INTRODUCTION:</b> Inflammation is a common pathological condition. On ...

'Antimicrobial peptides modulate lipopolysaccharide-induced gene expression of cytokines IL1β and IL10 and toll-like receptor 4 in rat blood leukocytes' - a Microbiology Independent Research Journal article on #ScienceOpen:

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🖇️ #Immunology #InflammationResearch

Scientists Uncover Hidden Patterns in COVID-Related Heart Inflammation All the science news you can handle in a single feed

Scientists Uncover Hidden Patterns in COVID-Related Heart Inflammation #Science #HealthandMedicine #Cardiology #COVID19 #HeartHealth #InflammationResearch