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• W4386002859 startingPage "126413" @default.
• W4386002859 abstract "PROteolysis Targeting Chimeras (PROTACs) showed tremendous therapeutic potential in degrading several oncoproteins including undruggable proteins. PROTACs are bifunctional molecules where one-part binds to target protein while the other end recruits protein degradation machinery. With the unveiling advancements in the field of PROTACs, we explored a combinatorial approach by developing antibody-based PROTAC (ABTAC) which may effectively degrade one of the key oncoprotein driving proliferation and progression of cancer - Epidermal growth factor receptor (EGFR). The objective of current research was to synthesize and characterize an EGFR degrading ABTAC for the treatment of non-small cell lung cancer (NSCLC). Cetuximab and pomalidomide (E3 ligase recruiting ligand) were conjugated using lysine conjugation and copper free azide-alkyne cycloaddition (CuAAC) click chemistry. Analytical characterization using reverse-phase liquid chromatography and mass spectrometry suggested conjugation of five E3-ligase inhibitor molecules/antibody. Nearly 10-30 folds reduction in IC50 was observed with ABTAC in HCC827 (EGFR sensitive) and H1650 (EGFR resistant) cells compared to cetuximab. Multicellular 3D spheroid assay strongly suggested that ABTAC induced significant apoptosis and also inhibited cell proliferation compared to control and antibody alone. Circular dichroism and surface plasmon resonance (SPR) confirmed minor alterations in the structure and receptor binding efficacy of the antibody post-conjugation." @default.
• W4386002859 created "2023-08-20" @default.
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• W4386002859 date "2023-12-01" @default.
• W4386002859 modified "2023-10-12" @default.
• W4386002859 title "Cetuximab-based PROteolysis targeting chimera for effectual downregulation of NSCLC with varied EGFR mutations" @default.
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• W4386002859 doi "https://doi.org/10.1016/j.ijbiomac.2023.126413" @default.
• W4386002859 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37598823" @default.
• W4386002859 hasPublicationYear "2023" @default.
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