Insilico Medicine’s latest AI-engineered drug ISM5411 could provide a novel approach for treating IBD

Alex Zhavoronkov, Ph.D.

Capping off a busy 2023, Insilico Medicine has announced a potentially first-in-class oral PHD inhibitor for the treatment of inflammatory bowel disease (IBD). ISM5411 is the fifth AI-backed drug candidate from Insilico Medicine to reach clinical stages.

ISM5411 targets prolyl hydroxylase domain (PHD) enzymes via modulation of the hypoxia-inducible factor (HIF) pathway, which is involved in cellular response to low oxygen levels. By inhibiting PHD, ISM5411 aims to stabilize HIF, thereby enhancing the expression of genes that help protect the gut lining and reduce inflammation.

AI’s role in ISM5411’s development

To develop ISM5411, InSilico tapped its AI platform, Pharma.AI. This involved deploying Chemistry42, a generative AI engine, which created the structure-based small molecule based on the PHD target protein structure. “After obtaining a series of lead compound…

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