Development of folate receptor targeting chimeras for cancer selective degradation of extracellular proteins
Year: 2024
Type: article
Abstract: Targeted protein degradation has emerged as a novel therapeutic modality to treat human diseases by utilizing the cell's own disposal systems to remove protein target. Significant clinical benefits have been observed for degrading many intracellular proteins. Recently, the degradation of extracellular proteins in the lysosome has been developed. However, there have been limited successes in selectively degrading protein targets in disease-relevant cells or tissues, which would greatly enhance the development of precision medicine. Additionally, most degraders are not readily available due to their complexity. We report a class of easily accessible Folate Receptor TArgeting Chimeras (FRTACs) to recruit the folate receptor, primarily expressed on malignant cells, to degrade extracellular soluble and membrane cancer-related proteins in vitro and in vivo. Our results indicate that FRTAC is a general platform for developing more precise and effective chemical probes and therapeutics for the study and treatment of cancers.
Source: Nature Communications
Institution: University of Wisconsin–Madison
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: U.S. Department of Health and Human Services, University of Wisconsin-Madison, University of Wisconsin Carbone Cancer Center, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, Division of Graduate Education, National Center for Research Resources, Center for Scientific Review
Awards: Creating a region- specific biomolecular atlas of the brain of Alzheimer’s disease, G1200757997, Acquisition of a High-Field Dual Source FTICR-MS for Pharmaceutical Research, G1712026730, Stress keratin 17 and CD4/8 ratio as prognostic markers in HIV-related anogenital squamous cell precancers and cancers (Biospecimens/Biocohort), G2118924489, G2284066598, G2388130288, G245808252, G2928873083, G3055837027, G3357070744, G3396811048, G3713652579, G3719356645, G4004214011, Development of Novel Antibody Conjugates for Cancer Immunotherapy, G42679306, G4687237281, G5339847549, G5628401499, G5813506420, DiLeu-enabled multiplexed quantitation for biomarker discovery and validation in Alzheimer’s disease, G6634682943, Mass Spectrometric Studies of Neuropeptides in Feeding, Acquisition of a High Resolution High Speed MALDI Mass Spectrometer for Biomedical Research at UW-Madison, Acquisition of a Dual-Source, High-Performance, Ion Mobility, Quadrupole Time-of-Flight Mass Spectrometry System for Biomedical Research at UW-Madison, G822836364, G885864977, G891322577, G9000041967, G9000127380, G9000197343, G9000231773, G9000265189, G9000352744, G925192949
OpenAlex ID: W4403233863