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SAH-EJ1 is a hydrocarbon-stapled peptide designed as a pan-ERBB inhibitor. It mimics the highly conserved juxta-membrane domain (JD) of the ErbB receptor family, which includes EGFR, HER2, and ErbB3. By acting in a dominant-negative fashion, SAH-EJ1 promotes the formation of non-functional ErbB dimers, thereby blocking both kinase-dependent and kinase-independent oncogenic signaling pathways. This mechanism leads to the inhibition of tumor growth and metastasis by inducing cell death through a combination of apoptotic and necrotic mechanisms, as well as disrupting mitochondrial function and calcium signaling. Developed by researchers at the University of Arizona and Arizona Cancer Therapeutics, SAH-EJ1 has demonstrated efficacy in preclinical models of glioblastoma, breast cancer, and lung cancer.
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