INCB3619

INCB3619 is a small molecule dual inhibitor of the disintegrin and metalloproteinase (ADAM) family members **ADAM10** and **ADAM17** (also known as TACE, TNF-alpha converting enzyme). By inhibiting these alpha-secretases, INCB3619 prevents the proteolytic cleavage and activation of various cell surface proteins, most notably the **Notch receptors** and ligands of the epidermal growth factor receptor (EGFR) family. In preclinical studies, it has demonstrated the ability to inhibit the growth of glioma stem cells by blocking Notch signaling and reducing the expression of hyperactive low-molecular-weight (LMW) Cyclin E. It also shows synergistic effects when combined with other targeted therapies, such as lapatinib in breast cancer models. Development of INCB3619 was primarily led by Incyte Corporation for the treatment of advanced malignancies.