Saruparib — Investigational Agent
Other · Phase 3 · AstraZeneca
Mechanism of Action
Saruparib is a next-generation, highly selective PARP1 inhibitor and PARP1-DNA trapper. Unlike first-generation PARP inhibitors that inhibit both PARP1 and PARP2, saruparib spares PARP2, which is implicated in the hematologic toxicity (anemia, thrombocytopenia) of the class. This selectivity preserves synthetic-lethal activity in homologous recombination repair (HRR)-deficient tumors while permitting higher, more sustained target coverage. The result is potent trapping of PARP1 on damaged DNA, generating cytotoxic double-strand breaks selectively in BRCA1/2- and PALB2-mutant cells.
Investigational Indications
- HR+/HER2- advanced breast cancer with BRCA1/BRCA2/PALB2 mutation
- HRR-deficient breast cancer
- BRCA-mutant ovarian cancer
- Metastatic castration-resistant prostate cancer with HRR alterations