The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.

01 Oct 2024·Redox Biology

The activity of therapeutic molecular cluster Ag5 is dependent on oxygen level and HIF-1 mediated signalling

Article

Author: Hacker, Lina ; Chalmers, Anthony J. ; Treder, Martin ; Sedgwick, Adam C ; Dominguez, Blanca ; Twigger, Sophie A ; Hammond, Ester M ; Hammond, Ester M. ; Porto, Vanesa ; Twigger, Sophie A. ; Sedgwick, Adam C. ; Chalmers, Anthony J ; Breckenridge, Ross ; Dominguez, Fernando

Regions of hypoxia occur in most solid tumours and are known to significantly impact therapy response and patient prognosis. Ag5 is a recently reported silver molecular cluster which inhibits both glutathione and thioredoxin signalling therefore limiting cellular antioxidant capacity. Ag5 treatment significantly reduces cell viability in a range of cancer cell lines with little to no impact on non-transformed cells. Characterisation of redox homeostasis in hypoxia demonstrated an increase in reactive oxygen species and glutathione albeit with different kinetics. Significant Ag5-mediated loss of viability was observed in a range of hypoxic conditions which mimic the tumour microenvironment however, this effect was reduced compared to normoxic conditions. Reduced sensitivity to Ag5 in hypoxia was attributed to HIF-1 mediated signalling to reduce PDH via PDK1/3 activity and changes in mitochondrial oxygen availability. Importantly, the addition of Ag5 significantly increased radiation-induced cell death in hypoxic conditions associated with radioresistance. Together, these data demonstrate Ag5 is a potent and cancer specific agent which could be used effectively in combination with radiotherapy.

01 Dec 2023·Biomedicine & Pharmacotherapy

AG5 is a potent non-steroidal anti-inflammatory and immune regulator that preserves innate immunity

Article

Author: Gutierrez-Adan, Alfonso ; Mingo-Casas, Patricia ; Argemí, Josepmaría ; Escribano-Romero, Estela ; Moreno, Alejandro ; Smerdou, Cristian ; Rey-Campos, Magalí ; Gonzalez, Gloria ; Lama, Raquel ; Figueras, Antonio ; Montoya, María ; Sanchez-Cordón, Pedro J ; Pineda-Lucena, Antonio ; Rivero-Buceta, Eva M ; Quesada-Gomez, Jose Manuel ; Miguel, Jesus San ; Saiz, Juan Carlos ; Martín-Acebes, Miguel A ; Botella-Asunción, Pablo ; Novoa, Beatriz ; Benlloch, Jose María ; Prosper, Felipe ; Vidaurre-Agut, Carla ; Mendoza, Laura

An archetypal anti-inflammatory compound against cytokine storm would inhibit it without suppressing the innate immune response. AG5, an anti-inflammatory compound, has been developed as synthetic derivative of andrographolide, which is highly absorbable and presents low toxicity. We found that the mechanism of action of AG5 is through the inhibition of caspase-1. Interestingly, we show with in vitro generated human monocyte derived dendritic cells that AG5 preserves innate immune response. AG5 minimizes inflammatory response in a mouse model of lipopolysaccharide (LPS)-induced lung injury and exhibits in vivo anti-inflammatory efficacy in the SARS-CoV-2-infected mouse model. AG5 opens up a new class of anti-inflammatories, since contrary to NSAIDs, AG5 is able to inhibit the cytokine storm, like dexamethasone, but, unlike corticosteroids, preserves adequately the innate immunity. This is critical at the early stages of any naïve infection, but particularly in SARS-CoV-2 infections. Furthermore, AG5 showed interesting antiviral activity against SARS-CoV-2 in humanized mice.

100 Deals associated with TMC-Ag5

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Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma	Preclinical	Spain	Arjuna Therapeutics	30 Apr 2025
Inflammation	Discovery	Spain	Polytechnic University of Valencia	31 Dec 2023

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