AI Achieves a Breakthrough in the Use of a New PHD Inhibitor to Cure Anaemia

New PHD Inhibitor to Cure Anaemia: AI Achieves a Breakthrough | The Lifesciences Magazine


InSilico Medicine (“InSilico”), a biotechnology company driven by generative artificial intelligence (AI) and in the clinical stage, announced today that its discovery of a novel PHD inhibitor for cure anaemia was published in the Journal of Medicinal Chemistry, an ACS Publications journal that focuses on critical studies about molecular structure and biological activity. Chemistry42, a unique generative chemistry platform with over 40 carefully chosen generative models, is the driving force behind this scholarly discovery.

Previous research has indicated that inhibiting prolyl hydroxylase domain enzymes (PHD) might impact basic biological processes, such as red blood cell synthesis, via controlling the HIF-α pathway, which has earned a Nobel prize. This suggests that PHD inhibition may have therapeutic promise to cure anaemia caused by chronic kidney disease.

New PHD Inhibitor to Cure Anaemia

With the aid of Chemistry42, Insilico’s scientists produced a number of molecule candidates after gathering structure data on the PHD target and existing molecules under the direction of a structure-based drug discovery (SBDD) strategy. Before a hit compound was created for additional optimisation, the AI-generated compounds were sorted and prioritised using built-in filters including drug-likeness, pharmacophore hints, synthesis evaluation, and more.

Thanks to Chemistry42, we had end-to-end assistance from molecule generation to hit compound selection. With the power of generative artificial intelligence, we could accelerate the drug discovery process without compromises in novelty or quality.”

Xiaoyu Ding, computational chemist sharing first authorship

Lead compound 15, which showed a positive in vitro/in vivo ADMET profile, a clear safety profile, and promising PK characteristics in several species, was the result of several rounds of synthesis test optimisation. Furthermore, the compound’s very easy production procedures were demonstrated to cure anaemia in a rat illness model.

Jianyu Xu, a medicinal chemist who co-authored the paper, stated, “Given that over 10% of the world’s population has chronic kidney disease, Insilico’s novel molecule could be a meaningful for further investigations and patients worldwide.” “After comprehensive research into PHD inhibitors already available on the market, we hope to develop a novel noncarboxylic acid molecule for better permeability and PK profiles.”

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