PARP1 PROTAC 180055 is a potent, PARP1-specific degradation PROTAC compound with DC50 of 180  nM and 240 nM in T47D and MDA-MB-231 cell lines, respectively.
180055 exhibits significant degradation potency towards PARP1 protein in 12 more cell lines, encompassing breast cancer cell lines (MDA-MB-468), ovarian cancer cell lines (IGROV1, A2780, Hey, CAOV1, OVK18, OC316, OVCAR3), colorectal cancer cell line (RKO), human acute T-lymphoblastic leukemia cell line (MOLT4), prostate cancer cell line (DU 145), as well as human osteosarcoma cell line (U-2 OS).
180055 is dependent on the ubiquitin-proteasome system, and does not affect other members of the PARP family, Tankyrase and PARP2.
180055 inhibits the catalytic activity of PARP1.
180055 protects cells from gene toxicity-induced cell death.
180055 (40 mg/kg) effectively degraded PARP1 in tumors derived from MOLT4-xenografted mice and mouse model of A2780 tumor xenografts with BRCA mutations, inhibits tumor growth.