DP Technology Achieves Breakthrough in Targeting Undruggable β-Catenin Using RiDYMO® Platform

In a significant advancement for cancer treatment, DP Technology's cutting-edge discovery platform, RiDYMO®, has managed to design a cyclic peptide that effectively targets β-catenin, which has traditionally been labeled as 'undruggable.' This remarkable feat was accomplished within a mere two months, showcasing the platform's efficiency and groundbreaking approach.

The Challenge of Targeting β-Catenin

The Wnt/β-catenin signaling pathway plays a vital role in several biological functions and has been linked to the development of various cancers. Despite its importance as a potential target for therapies, β-catenin has resisted drug discovery efforts due to its flat protein surface, which renders it difficult to inhibit.

Harnessing AI and Advanced Techniques

DP Technology’s RiDYMO® platform employs artificial intelligence and several innovative methodologies to tackle such formidable targets. By utilizing a vast library of over 10^12 cyclic peptides and macrocyclic molecules—comprising both natural and artificial amino acids—researchers were able to identify and optimize molecular interactions efficiently.

The Process

The process involved several critical steps:
1. Optimizing the β-Catenin Structure: Enhancements were made to improve the binding interface with cyclic peptides.
2. High-Throughput Screening: The platform's extensive library facilitated rapid screening, enabling the identification of promising candidates.
3. Synthesis and Testing: A total of 29 candidate molecules were synthesized and evaluated, with impressive results emerging from the tests.

Promising Results

Among the synthesized candidates, a total of 12 exhibited powerful inhibition of the targeted protein interactions with an IC50 value of less than or equal to 10 μM—resulting in an extraordinary success rate exceeding 40%.
One compound, specifically designated as compound 24, showcased significant abilities in binding to β-catenin while disrupting its interaction with BCL9 and inhibiting the Wnt/β-catenin signaling pathway.

Dr. Dongdong Wang, Co-President of the Drug Discovery Unit at DP Technology, articulated the platform's prowess in addressing previously challenging targets and underscored the rapid design of high-quality compounds. The success seen with β-catenin could be a pivotal moment for the pharmaceutical industry, potentially accelerating the creation of orally available cyclic peptide drugs.

The Future of Drug Discovery

This groundbreaking achievement in cyclic peptide design highlights the transformative power of AI-driven platforms in drug discovery. By overcoming the challenges posed by 'undruggable' targets, DP Technology is poised to open new avenues in cancer treatment and possibly a wider range of therapeutic areas.

About RiDYMO®

RiDYMO® is an advanced platform that combines the principles of artificial intelligence with sophisticated drug discovery techniques. It has been instrumental in designing not only cyclic peptides but has also played a role in developing small molecule compounds targeting essential proteins, such as c-Myc and GPX4. Using tools such as the proprietary Hermite® computational drug design software, RiDYMO® offers an innovative pathway for tackling some of the most persistent challenges in drug design.

In conclusion, the collaboration between advanced computational methods and drug discovery initiatives demonstrates a promising future. DP Technology’s RiDYMO® has not only shown its capabilities but has also set a new standard to redefine the limits of drug discovery, aiming to yield effective treatments for complex diseases like cancer.