PLX038A

PLX038A is a **long-acting, pegylated prodrug of SN-38**, designed to prolong the half-life and controlled release of SN-38, the active metabolite of irinotecan and sacituzumab govitecan. SN-38 is a potent **topoisomerase 1 inhibitor** that induces replication stress, inhibits DNA synthesis, and causes DNA damage leading to cell death in cancer cells. PLX038A consists of a 15 nm, 4-arm, 40 kDa PEG scaffold covalently linked via cleavable linkers to four SN-38 molecules, allowing slow and sustained SN-38 release. This structure improves accumulation in tumors (including penetrating the blood-tumor-brain barrier), increases efficacy, and reduces toxicity compared to non-pegylated agents. PLX038A exploits synthetic lethality in cancers with defective DNA damage response (DDR) and demonstrates synergy with DDR inhibitors such as PARP inhibitors (e.g. rucaparib, talazoparib). It has shown preclinical and early clinical activity in ovarian cancer, central nervous system tumors, triple-negative breast cancer, glioblastoma, and other advanced solid tumors[1][2][3][4][5][6][7].

Brand names

PLX038APLX-038APLX 038A

Other names

PLX038APLX-038APLX 038APEG~SN-38