DDO3602 is a potent, effective small molecule HSP90-mediated proteolysis-targeting chimera (HSPTAC) degrader of PARP1 with DC50 of 490.3 nM in MCF-7 cells, induces PARP1 degradation through a multi-E3 ubiquitin ligase-mediated degradation pathway.
DDO3602 effectively degrades PARP1 levels by 69.7% at a concentration of 1 μM.
DDO3602 exhibits significant MCF-7 antiproliferative activity (IC50 = 187 nM) for MCF-7 cells.
DDO3602 recruits multiple E3 ubiquitin ligases, including such as tripartite motif-containing protein 25 (TRIM25), ubiquitin protein ligase 5 (UBR5), Myc-binding protein 2 (MYCBP2), membrane-associated RING finger protein 5 (MARCHF5), and tripartite motif-containing protein 50 (TRIM50), thereby promoting PARP1 degradation via a UPS-dependent manner.
DDO3602 effectively induces G2/M cell cycle arrest and DNA damage.
DDO3602 inhibits the migration of MCF-7 cells and exhibits effective anticancer activity in the MCF-7 xenograft tumor mouse model.