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Overview
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Background
MK-0752 is a potent gamma secretase inhibitor in clinical development (IC50 ~50 nM). Gamma secretase is an important component in the NOTCH cleavage machinery that catalyzes the cleavage of receptor protein substrates within their transmembrane domain. Inhibition of Notch inhibits BC cell proliferation in vitro. Notch signaling requires gamma secretase, which cleaves Notch, releasing the Notch intracellular domain (NICD) to activate transcription of target genes. NOTCH signaling plays an important role in normal tissue development, cell fate determination, proliferation, and survival. NOTCH signaling is activated following the binding of cognate ligands that include Delta1, Delta2, and Delta3 and Jagged1 and Jagged2.
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