Grove Biopharma's Protein-Like Polymers Successfully Degrade Undruggable Cancer Targets MYC and KRAS
核心洞察
Grove Biopharma (搜索) published preclinical results in Nature Communications demonstrating successful targeted degradation of MYC (搜索) and KRAS (搜索) oncogenic drivers using protein-like polymers.
The study shows PLPs can degrade MYC (搜索), an intrinsically disordered transcription factor underlying approximately 70% of human cancers that has eluded conventional drug approaches.
The Bionic Biologics platform creates bifunctional molecules that simultaneously engage target proteins and cellular degradation machinery, representing a novel therapeutic modality.
Grove Biopharma (搜索) announced the publication of preclinical results in Nature Communications demonstrating successful targeted degradation of two critical oncogenic drivers, MYC (搜索) and KRAS (搜索), using its novel protein-like polymers (PLPs) platform. The peer-reviewed study, titled "Heterobifunctional proteomimetic polymers for targeted degradation of MYC and KRAS," represents a significant breakthrough in targeting previously undruggable cancer proteins.
Breakthrough in Targeting Undruggable Oncogenes
The study demonstrates the ability of PLPs to degrade MYC (搜索), an intrinsically disordered transcription factor that underlies approximately 70% of all human cancers and has long eluded both small molecule and antibody-based approaches. The research establishes that PLPs can be engineered to be bifunctional, enabling simultaneous engagement of MYC and the cell's proteolytic machinery to achieve selective, targeted degradation.
"MYC (搜索) and KRAS (搜索) drive a significant portion of human cancers – often aggressive ones – and effective drugs against these targets remain extremely limited," said Nathan Gianneschi, Ph.D., Principal Investigator on the study, Professor at Northwestern University and Scientific Founder of Grove Biopharma (搜索). "We invented a one-step polymer chemistry solution in which protein-like polymers engage disordered proteins and recruit the cell's own degradation machinery. This had not been done previously, and it proved effective against some of the most challenging targets in cancer biology."
Platform Versatility and Mechanism of Action
The study also establishes platform versatility through successful degradation of KRAS (搜索), another foundational oncogenic driver, and by engaging multiple cellular degradation pathways. By functioning as targeted protein degraders rather than inhibitors, PLPs eliminate pathogenic proteins entirely. Unlike antibodies or traditional small molecules, PLPs combine the selectivity of biologics with the ability to enter cells and induce intracellular protein–protein interactions.
Gianneschi's team developed PLPs that selectively bind MYC (搜索) and KRAS (搜索) and can direct each target to the cell's natural degradation pathways, resulting in cancer cell death. The approach represents a novel therapeutic strategy for proximity-based therapeutics in cancer.
Bionic Biologics Platform Technology
Grove Biopharma (搜索)'s Bionic Biologics platform integrates advances in synthetic precision polymerization, cutting-edge computational and experimental protein/peptide engineering, and medicinal chemistry to create protein-scale molecules capable of targeting disease-driving proteins, including those that lack well-defined binding pockets characterized by intrinsically disordered regions.
"Successful degradation of both MYC (搜索) and KRAS (搜索) highlights PLPs' proximity-induced chemistry as an effective and generalizable mechanism for targeting proteins beyond the reach of traditional therapeutic modalities," said Paul Bertin, Ph.D., Co-Founder, President and Chief Technology Officer at Grove Biopharma (搜索). "Our Bionic Biologics platform generates fully synthetic, rationally designed protein mimetics that overcome the major limitations of conventional biologics and peptides."
Therapeutic Development and Future Applications
Grove Biopharma (搜索) has licensed the intellectual property for this technology from Northwestern University and is accelerating translation toward therapeutic development. While the current study focused on cancer, Grove is also advancing PLPs to target proteins implicated in neurodegenerative, inflammatory, and metabolic diseases.
The company is developing biologics with properties that support oral bioavailability and, in some cases, penetration of the blood-brain barrier. Because PLPs are modular, cell-permeable, and scalable to manufacture, they enable rapid, iterative design-build-test cycles, allowing the company to quickly identify lead molecules for challenging intracellular targets.