A polypeptide-based (‘bioPROTAC’) technology designed to degrade the MYC oncoprotein inside cells, applicable in cancer treatment and prevention
Proposed Use
This technology has application in cancer therapy, specifically targeting MYC-driven cancers. MYC is overexpressed in most human cancers, making it a critical target for therapeutic intervention. An intrinsically disordered warhead derived from MYC’s Compaction Region 1 (CR1) can be used to target MYC for irreversible intracellular degradation, leading to tumour regression. This approach is particularly promising for treating cancers such as liver cancer, leukaemia, lymphoma, and various solid tumours.
The technology’s ability to selectively degrade MYC offers a novel and effective strategy for cancer treatment, potentially improving patient outcomes and reducing mortality rates .
Problem Addressed
MYC is a transcription factor overexpressed in most human cancers, driving tumour growth and progression. Despite its critical role in cancer, MYC has been considered “undruggable” due to its intrinsically disordered structure, which lacks binding pockets for conventional drugs. This presents a significant challenge in developing effective therapies targeting MYC. The novel polypeptides derived from MYC’s Compaction Region 1 (CR1) address this problem by leveraging previously unknown self-interaction properties of CR1. These polypeptides can be employed as “warheads” in bioPROTACs (Proteolysis-Targeting Chimeras) to selectively degrade MYC in cancer cells. This approach not only neutralizes MYC’s oncogenic activity but also offers a new pathway for developing anti-MYC therapies, potentially transforming cancer treatment and improving patient survival rates.
Technology Overview
The technology involves polypeptides derived from the Compaction Region 1 (CR1) of the MYC oncoprotein. CR1 exhibits strong selectivity for MYC, making it a viable target for therapeutic intervention. A fusion of CR1 with ubiquitin ligases to create bioPROTACs, which target MYC for proteasomal degradation. Experimental data demonstrate the effectiveness of CR1-based bioPROTACs in degrading MYC and inhibiting its transcriptional activity. This technology offers a novel approach to cancer therapy by targeting a previously “undruggable” protein, providing a new avenue for developing treatments for MYC-driven cancers. The flexibility and specificity of CR1-based polypeptides make them a promising tool for both diagnostic and therapeutic applications in oncology.
Benefits
- Targeted Therapy: Efficiently degrades MYC in cancer cells by channelling overexpressed MYC into the intracellular protein destruction machinery
- Novel Approach: Addresses the “undruggable” nature of MYC.
- Effective Degradation: Based on a bioPROTAC design for efficient intracellular MYC degradation.
- Broad Applicability: Suitable for various types of cancer.
- Improved Outcomes: Potentially enhances patient survival rates.
- Therapeutic Versatility: Applicable in both monotherapy and combination therapy.
Intellectual property information
GB Priority Application filed Nov 2024 – 2417594.5 – Cancer
