ArticleFrontiers in immunology2023
Targeted degradation of MERTK and other TAM receptor paralogs by heterobifunctional targeted protein degraders.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- A receptor-Fc based SFV replicon Trim-Away platform for targeted viral protein degradation.Virology journal · 2026Article
- MerTK Is Regulated by Orphan Nuclear Receptor 4A1 (NR4A1) and NR4A2 in Colon Cancer Cells.Cancers · 2026Article
- A Gold-PROTAC Degrades the Oncogenic Tyrosine Kinase MERTK: Insights into the Degradome from a Steady-State System.ACS chemical biology · 2026Article
- Nogo-B impairs efferocytosis in monocyte-derived macrophages and exacerbates septic liver injury.JHEP reports : innovation in hepatology · 2025Article
- Exploring tumor-associated macrophages in glioblastoma: from diversity to therapy.NPJ precision oncology · 2025Review
- Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer.Cell communication and signaling : CCS · 2025Review
- Establishing Tyro3, Axl, and Mertk Chinese hamster ovary (CHO) reporter cell lines for cancer immunology and therapeutic applications.Methods in cell biology · 2025Article
- Review
- MERTK Inhibition as a Targeted Novel Cancer Therapy.International journal of molecular sciences · 2024Review
- The Tolerogenic Influence of Dexamethasone on Dendritic Cells Is Accompanied by the Induction of Efferocytosis, Promoted by MERTK.International journal of molecular sciences · 2023Article
- Soluble TAM Receptor Tyrosine Kinases Correlate with Disease Severity and Predict the Early Responsiveness of Sublingual Immunotherapy in Allergic Rhinitis.Journal of inflammation research · 2023Article
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Authors and funding
11 authors.
Funding
Abstract
TAM receptors (TYRO3, AXL, and MERTK) comprise a family of homologous receptor tyrosine kinases (RTK) that are expressed across a range of liquid and solid tumors where they contribute to both oncogenic signaling to promote tumor proliferation and survival, as well as expressed on myeloid and immune cells where they function to suppress host anti-tumor immunity. In recent years, several strategies have been employed to inhibit TAM kinases, most notably small molecule tyrosine kinase inhibitors and inhibitory neutralizing monoclonal antibodies (mAbs) that block receptor dimerization. Targeted protein degraders (TPD) use the ubiquitin proteasome pathway to redirect E3 ubiquitin ligase activity and target specific proteins for degradation. Here we employ first-in-class TPDs specific for MERTK/TAMs that consist of a cereblon E3 ligase binder linked to a tyrosine kinase inhibitor targeting MERTK and/or AXL and TYRO3. A series of MERTK TPDs were designed and investigated for their capacity to selectively degrade MERTK chimeric receptors, reduce surface expression on primary efferocytic bone marrow-derived macrophages, and impact on functional reduction in efferocytosis (clearance of apoptotic cells). We demonstrate proof-of-concept and establish that TPDs can be tailored to either selectivity degrades MERTK or concurrently degrade multiple TAMs and modulate receptor expression
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