Anemia Treatment with PHD Inhibitor

A new PHD inhibitor for the treatment of anemia has been discovered, according to a study published in the Journal of Medicinal Chemistry.

Image Credit: ART-ur/Shutterstock.com Animal Iron Deficiency Anemia

Chemistry42, a unique generative chemistry platform developed by InSilico Medicine that includes over 40 carefully chosen generative models, powers this platform.

Previous research has indicated that inhibiting prolyl hydroxylase domain enzymes (PHD) can regulate the HIF-α pathway, which in turn affects basic biological processes such as the generation of red blood cells. This suggests that PHD could be used as a treatment for anemia caused by CKD.

With the aid of Chemistry42, Insilico’s scientists produced several molecule candidates by gathering structural data on the PHD target and existing compounds, all in accordance with a structure-based drug discovery (SBDD) approach.

Before a hit compound was created for additional optimization, the AI-generated compounds were sorted and prioritized using built-in filters, including drug-likeness, pharmacophore clues, synthesis assessment, 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, Study First Author, InSilico Medicine

Lead compound 15, which showed a positive in vitro/in vivo ADMET profile, a clear safety profile, and promising PK characteristics in various species, was the result of numerous rounds of synthesis test optimization. Furthermore, the compound’s very easy production procedures were demonstrated to reduce anemia in a rat disease model.

Given that more than 10% of the global population suffers from CKD, Insilico’s novel molecule could be 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.

Jianyu Xu, Study Co-Author, InSilico Medicine

Xu, J., et. al. (2024) Discovery of Novel and Potent Prolyl Hydroxylase Domain-Containing Protein (PHD) Inhibitors for The Treatment of Anemia. Journal of Medicinal Chemistry. doi:10.1021/acs.jmedchem.3c01932

Do you have a review, update or anything you would like to add to this news story?

As part of an Editorial short series, AZoRobotics takes a look at how the renewable energy sector is harnessing the power of robotic technologies. Here, we take a look at robots in hydropower stations.

Amid the rapid global expansion of the wind energy sector, the integration of robotics is becoming pivotal for wind farm operators.

Like any renewable energy infrastructure, solar plants must be protected and secured. It is here where robots and autonomous systems can come into play.

Discover Cavitar’s welding cameras that can be used in a variety of situations to offer high-quality visualization of the welding processes.

MTI’s 1510A portable signal generator and calibrator is ideal for testing the integrity of sensor signal conditioning electronics.

Using the advantages of the phased array technology, Olympus has designed a powerful inspection system for seamless pipe inspections well-adapted to the stringent requirements of the oil and gas markets. This phased array system is flexible and can be used to match inspection performances and the product requirements of customers.

AZoRobotics.com - An AZoNetwork Site