MASTL-IN-3

**MASTL-IN-3 (compound 60)** is a potent, selective small-molecule inhibitor of microtubule-associated serine/threonine kinase-like (MASTL), a kinase overexpressed in various cancers including breast, colorectal, and acute myeloid leukemia, where it promotes proliferation, metastasis, and therapy resistance via inhibition of protein phosphatase 2A (PP2A). By blocking MASTL kinase activity, it reactivates PP2A, leading to dephosphorylation of substrates like ENSA, mitotic defects, reduced c-Myc stability, and enhanced sensitivity to radiotherapy and chemotherapy. Demonstrated anti-proliferative effects in cancer cell lines with a pIC50 of 9.10, positioning it as a potential first-in-class therapeutic for oncology, particularly in combination regimens.[10]