R+D CSIC

A new non-steroidal anti-inflammatory and immune regulator that can replace corticosteroids has been developed

Created by a team led by the CSIC and the UPV, it is capable of inhibiting the cytokine storm associated with severe inflammation while preserving innate immunity. It is a synthetic derivative of andrographolide, the active ingredient of the plant Andrographis paniculate, commonly known as kalmegh or King of Bitters. It may also be useful in the treatment of rheumatoid arthritis, Crohn's disease, lung inflammation and fatty liver disease.

A multidisciplinary research team composed of several CSIC institutes, the Universitat Politècnica de València (UPV), and other academic and clinical institutions, has developed a new anti-inflammatory which has fewer adverse effects and less toxicity than corticosteroids and, more interesting, unlike corticosteroids, preserves the innate immune system.

The compound, called AG5, is a synthetic sulphonic derivative of andrographolide, the active ingredient of the plant Andrographis paniculata, commonly known as kalmegh or King of Bitters, endemic to certain regions of India, Sri Lanka and other areas of Southeast Asia. From a therapeutic point of view, the AG5 derivative has significant advantages, as it significantly increases anti-inflammatory activity, while also improving the pharmacokinetic profile.

This new compound is a potential substitute for dexamethasone (and corticosteroids in general), with far fewer adverse effects and toxicity, while preserving the immune system.

New class of anti-inflammatory drugs

According to the researchers, the main novelty of AG5 is that it initiates a new class of anti-inflammatory drugs. AG5 can inhibit the cytokine storm (one of the most severe symptoms of COVID-19 and other pathologies, associated with overreaction of the immune system), like corticosteroids.

However, unlike the latter, AG5 preserves the patient's innate immunity. This is essential in the early stages of any new infection, as the body needs to develop a defensive response against the new pathogen, but also in the treatment of many types of cancer, where suppression of the primary immune response facilitates tumour development.

The AG5 compound has already been tested in several animal models, proving its usefulness in inhibiting one of the most severe effects of inflammatory processes associated with infections such as COVID-19, cancer and other chronic inflammatory diseases. The results, which include several patents, have been published in Biomedicine and Pharmacotherapy.

The preclinical research is almost complete, including toxicological studies in various animal models, and scaling for industrial production is underway

Clinical trial for fatty liver starting in 2024

The team hopes that AG5 will also be useful in the treatment of chronic inflammatory diseases such as rheumatoid arthritis, Crohn's disease, lung inflammation and fatty liver disease.

AG5 has also been proposed for the prevention and treatment of cytokine storm in cancer T-cell therapy (CAR-T). The results of AG5 have led to a Spanish patent approved in 2023, which is currently under extension in Europe and North America. Another European patent has recently been filed.

Currently, preclinical research is almost complete, including toxicology studies in different validated animal models, and scale-up for industrial production is ongoing. In 2024, the research team foresees an application to the Spanish Agency for Medicines and Health Products (AEMPS) for phase I and II clinical trials in fatty liver disease therapy.

Developed in response to the COVID-19 pandemic

During the COVID-19 pandemic, clinical trials in hospitalized patients confirmed that corticoids like dexamethasone reduced mortality, but were detrimental when administered at the onset of infection symptoms. This is because the strong immunosuppressive activity of corticoid drugs weakens the primary immune response, causing a delay in infection clearance and adverse outcomes in severe viral pneumonias.

 In this scenario, in March 2020, the CSIC organized an Interdisciplinary Thematic Platform called Global Health (PTI Salud Global, in Spanish), bringing together more than 400 researchers from 144 research groups to address the challenges posed by the coronavirus epidemic, from social to therapeutic aspects."

It was within the framework of this platform that AG5 was developed. The multidisciplinary team, composed of scientists from the CSIC, the Universitat Politècnica de València, and other academic and clinical institutions, was led by CSIC researchers José María Benlloch (Institute of Instrumentation for Molecular Imaging, CSIC-UPV), and Pablo Botella (Institute of Chemical Technology, CSIC-UPV).

Contact:

Marc Escamilla
Vicepresidencia Adjunta
de Innovación y Transferencia - CSIC
Tel.: 96 161 29 95
Correo-e: This email address is being protected from spambots. You need JavaScript enabled to view it.

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