PP5-IN-2 is an orally active and selective protein phosphatase 5 ( PP5 ) inhibitor with an IC 50 value of 0.9 μM. PP5-IN-2 activates p53 and downregulates cyclin D1 and MGMT , which shows potency in cell cycle arrest and reverses Temozolomide (TMZ) resistance in the U87 MG cell line. PP5-IN-2 effectively inhibits tumor growth in the xenograft mouse model.