UNC0379

UNC0379 is a **selective, substrate-competitive small molecule inhibitor** of the lysine methyltransferase **SETD8** (also known as PR-Set7/KMT5A)[5][7][8]. It acts by competitively inhibiting the peptide substrate binding site of SETD8 with an IC50 of approximately 7.3–9.0 μM, and it is highly selective over at least 15 other methyltransferases[5][8]. Mechanistically, UNC0379 inhibits methylation of histone H4 at lysine 20 (H4K20me1), which disrupts DNA damage repair, increases DNA damage, and activates the p53 pathway, leading to increased apoptosis in cancer cells[3][4][1]. UNC0379 has been studied for sensitizing cancer cells—such as neuroblastoma, glioblastoma, cervical cancer, and multiple myeloma—to standard chemotherapeutics like cisplatin and melphalan[1][3][4][6]. It acts synergistically with drugs such as cisplatin and adavosertib and can inhibit colony formation and tumor growth in both in vitro and in vivo models[1][3][4]. UNC0379 is intended for **research use only** and not approved for clinical use.

Brand names

UNC0379UNC-0379UNC 0379

Other names

UNC0379UNC-0379UNC 0379