Enabling Metabolic Disease Research With DNA-encoded Library Screening: Case Study on HAO1
For numerous rare diseases, the steep costs associated with drug discovery and limited patient populations pose significant obstacles to the advancement of treatments. The DNA-encoded discovery platform presents a swift and cost-effective approach to identifying promising candidates, thereby facilitating drug discovery efforts for complex targets, including those relevant to rare diseases. Primary hyperoxaluria type 1 (PH1) is a rare inherited liver disorder affecting glyoxylate metabolism. Targeting hydroxy acid oxidase 1 (HAO1) as a strategy can reduce the buildup of toxic oxalate, offering a potential cure for PH1. Leveraging the DNA-encoded discovery platform, our team successfully identified multiple new chemical series of potent HAO1 binders. Through medicinal chemistry optimization, we enhanced these compounds’ potency and their absorption, distribution, metabolism, excretion (ADME), and pharmacokinetic (PK) profiles. This case study underscores the efficacy of this discovery approach in accelerating therapy development timelines and improving the success rate of identifying lead compounds for rare diseases, offering significant promise for entities focused on these challenging therapeutic areas.
This poster is presented at Rare Drug Development Symposium 2024.
