JMC｜Insilico Medicine nominates novel AI-driven PHD inhibitor targeting anemia

Clinical stage generative artificial intelligence (AI)-driven biotechnology company InSilico Medicine (“InSilico”), today announced that the Journal of Medicinal Chemistry, an ACS Publications journal focusing on critical studies about molecular structure and biological activity, has published the company’s discovery of a novel PHD inhibitor for the treatment of anemia. The academic breakthrough is powered by Chemistry42, its proprietary generative chemistry platform consisting of more than 40 selected generative models.

As suggested in previous studies, the inhibition of prolyl hydroxylase domain enzymes (PHD) influences fundamental biological processes, including red blood cell production by regulating the Nobel prize-winning HIF-α pathway, thus indicating potential for the treatment of CKD-induced anemia.

Guided by a structure-based drug discovery (SBDD) strategy, Insilico’s scientists gathered structure information on the PHD target and known molecules, and generated series of molecule candidates with the help of Chemistry42. Utilizing built-in filters covering drug-likeness, pharmacophore clues, synthesis evaluation and more, the AI-generated candidates were ranked and prioritized before a hit compound was produced for further optimization.

“Thanks to Chemistry42, we had end-to-end assistance from molecule generation to hit compound selection,” said Xiaoyu Ding, the computational chemist sharing first authorship. “With the power of generative artificial intelligence, we could accelerate the drug discovery process without compromises in novelty or quality.”

Afterward, several rounds of synthesis test optimization yielded lead compound 15, which demonstrated a favorable in vitro/in vivo ADMET profile, a clean safety profile, and promising PK properties in multiple species. Moreover, the compound was proven to alleviate anemia in a rat disease model, with relatively simple synthesis steps.

“Given that more than 10% of the global population suffers from CKD, Insilico’s novel molecule could be a meaningful for further investigations and patients worldwide,” said Jianyu Xu, the medicinal chemist who co-authored the paper. “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.”

About Insilico Medicine

Insilico Medicine, a global clinical stage biotechnology company powered by generative AI, is connecting biology, chemistry, and clinical trials analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques for novel target discovery and the generation of novel molecular structures with desired properties. Insilico Medicine is developing breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases, infectious diseases, autoimmune diseases, and aging-related diseases. www.insilico.co