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NACK inhibitors are a class of small molecules developed by StemSynergy Therapeutics that target the Notch signaling pathway by inhibiting the Notch Activation Complex Kinase (NACK). NACK is a critical co-activator that associates with the Notch intracellular domain (NICD) and the DNA-binding protein CSL to facilitate the recruitment of the transcriptional machinery required for Notch target gene expression. By disrupting this interaction, NACK inhibitors effectively block Notch-mediated oncogenic signaling. This therapeutic approach is being investigated for the treatment of Notch-driven malignancies, including T-cell acute lymphoblastic leukemia (T-ALL) and various solid tumors where Notch signaling is aberrantly activated.
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