Progenra has discovered unique Molecular Glues (MGs) and PROTAC drugs by employing novel ubiquitin ligases other than cereblon and VHL ligases. Progenra has established new MOA and wholly owned IP position on novel MGs and PROTACs. Progenra is also at the forefront of discovering and developing molecular glues, molecules that bind to ubiquitin ligases and change ubiquitination properties of the E3 ligases. Progenra has discovered potent inhibitors and activators of ubiquitin proteasome system therapeutic targets associated with various diseases including cancer, inflammatory disease, neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and cardiovascular disease.
Molecular Glues for Neurodegenerative Diseases
Targeting mitophagy and protein aggregation
Dysfunction in the protein and organelle degradation system is believed to underlie most forms of neurodegenerative disease. In Alzheimer’s disease and Parkinson’s disease, protein aggregation, in conjunction with accumulation of defective mitochondria, leads to neuronal death. Progenra is developing molecular glues and PROTAC drug candidates that promote mitophagy and reduce pathogenic protein aggregation. Small molecules discovered by Progenra constitute a breakthrough MOA and a novel approach to treating neurodegenerative diseases.
Inflammatory signal pathways are regulated at various points by E3 ligases. Progenra has developed Molecular Glue compounds that show in vivo anti-inflammatory activity in psoriasis and asthma models that is currently in preclinical development. We are also developing novel Molecular Glues (MGs) and PROTACs against proinflammatory target proteins for advancing them as anti-inflammatory agents.
More than 30 percent of all human cancers – including 95 percent of pancreatic cancers and 45 percent of colorectal cancers — are driven by mutations of the RAS family of genes. It is well known that RAS family of proteins are prone to drug resistance with covalent or non-covalent monotherapies. Other companies are developing K-RAS PROTACs by utilizing cereblon and VHL ligands, a crowded and chemically well explored strategy that does not offer freedom to operate. Progenra has adopted a unique approach by exploiting a novel ubiquitin E3 ligase that is associated with plasma membrane. Progenra K-RAS PROTACs are highly effective and potent in degrading K-RAS derivatives.
Targeting Tyrosine Kinase Receptors and Membrane Proteins with unique PROTACs
Most of Pharma and Biotech PROTAC Strategies are focused on cereblon (VHL, HDM2 ligases). Big roadblocks exist with IP issues and cereblon-based PROTACs are not suitable for chronic non-oncology applications due to potential teratogenic risks of cereblon binders. There no membrane associated ubiquitin ligases exploited for membrane protein degradation. A membrane ubiquitin ligase that is associated with Receptor Tyrosine Kinases and PROTACs developed by this ligase are highly potent as compared to other ligands in the field. Progenra team is excited by the unique approach that stands apart from the industry and offers potency and selectivity and IP position not available with other molecules under development.