Meet the Company Using Artificial Intelligence for Designing Targeted Protein Degraders
Proteins are essential components of living matter – they function as building blocks for cells and tissues, as well as participate in signaling and practically all biochemical activities. However, each protein operates correctly only for a limited amount of time and is eliminated by molecular machinery after it has reached its “functional shelflife”. To maintain a healthy and functional proteome, cells tightly control protein turnover processes, ensuring that misfolded, damaged, and old proteins exit the game in a timely manner. This sophisticated mechanism of degradation was recently hijacked by the drug discovery industry to develop new small molecule therapies — protein degraders.
The excitement about targeted protein degraders has been growing rapidly – since the application of targeted protein degradation (TPD) to drug discovery was first introduced by the publication of three landmark papers in 2015. According to Nello Mainolfi, CEO of Kymera Therapeutics, practically every big pharma player and every medium-sized biotech business has recently started internal R&D research or external collaborations in the field of protein degraders.
One company that is at the cutting edge of protein degradation research is Celeris Therapeutics, which has built a sophisticated artificial intelligence (AI)-based platform to be able to design novel targeted protein degradation therapeutics more rapidly, at lower cost, and with a higher probability of success.
Celeris Therapeutics was founded in Graz, Austria, in 2021 and is headquartered in Silicon Valley, California. The company expanded rapidly and became a unique player in the emerging field of targeted protein degradation. The company has received $6 million to date from a number of venture capitalists, including R42, APEX Ventures, Pace Ventures Enigma, i&i biotech and longevitytech.fund.
In contrast to the discovery of "traditional drugs" such as small molecule inhibitors and most biologics, the development of protein degraders presents unique challenges as degraders are acting with an event-driven pharmacology. For example, the ubiquitin proteasome system (UPS) can be exploited to tag a protein via ubiquitin and degrade it through the proteasome.
The complexity in this therapeutic modality is significantly increased due to a higher number of degrees of freedom compared to occupancy-driven pharmacology. For example, topics such as expression profiles of E3 ligases in different tissues or accessibility of pathogenic proteins to the UPS need to be considered in the earliest drug design stages.
Figure 1: Illustration demonstrating the mode of action of the ubiquitin-proteasome system.
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