MK-8242 + cytarabine

MK-8242 + cytarabine is a combination therapy under clinical investigation for the treatment of **refractory or recurrent acute myelogenous leukemia (AML)**. - **MK-8242** is a potent, orally bioavailable **small molecule inhibitor of human double minute 2 (HDM2/MDM2)**, which binds and inhibits MDM2, preventing its negative regulation of the tumor suppressor protein TP53. By disrupting the MDM2:TP53 interaction, MK-8242 stabilizes and activates TP53, leading to growth arrest or apoptosis in TP53 wild-type cancer cells[2][5][7]. - **Cytarabine** is a cytotoxic nucleoside analog that inhibits DNA synthesis, commonly used in AML treatment. - Preclinical studies have shown MK-8242 can sensitize cells to cytarabine, providing rationale for combination therapy[6]. - The combination is given in cycles, typically with MK-8242 administered orally on Days 1–7 and cytarabine on Days 1–4 of a 21-day cycle to permit bone marrow recovery and minimize overlapping toxicity[1][6]. - No approved formulation or trade name exists for this combination; it remains in clinical trial development.