Potent drug candidate could transform liver disease treatment

Human liver

Scientists from Gwangju Institute of Science and Technology in Korea have discovered compound 11c, a potentially ground-breaking oral treatment for metabolic dysfunction-associated steatohepatitis.

Their research signals a transformative leap in liver disease management, addressing both inflammation and fibrosis.

11c exhibited potent anti-inflammatory and fibrotic effects and high levels of safety in animal models. It is progressing to Phase I clinical trials with JD Bioscience.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a burgeoning global health concern, posing a significant threat to public health and escalating the burden on healthcare resources.

Characterised by the accumulation of fat in the liver, MASLD increases the risk of progressing to more severe conditions such as metabolic dysfunction-associated steatohepatitis (MASH), which is marked by inflammation, ballooning, and potential fibrosis.

In response to the pressing need of effective treatments for these metabolic disorders, researchers led by Professor Jin Hee Ahn from Gwangju Institute of Science and Technology (GIST) meticulously developed compound 11c, a novel peripheral 5HT2A antagonist.

Dr Haushabhau Shivaji Pagire, first author and senior researcher at the Medicinal Chemistry Laboratory at GIST, said: “Our meticulous analyses have revealed a significant reduction in inflammatory and fibrosis markers, attesting to the potent anti-inflammatory and fibrotic effect of the compound. This action, targeting both inflammation and fibrosis, is a promising step forward in treating MASH.”

Beyond its therapeutic potential and pharmacokinetic attributes, including over 60% oral bioavailability, compound 11c exhibits hepatocyte and plasma stability, minimal cytotoxicity, and low cytochrome P450 inhibition.

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