BER-IN-1 is a base excision repair (BER) inhibitor that specifically targets DNA apurinic/apyrimidinic (abasic) sites. It works by disrupting the BER pathway through β-elimination and β,δ-elimination cleavage at these sites, leading to DNA double-strand breaks (DSBs). BER-IN-1 enhances the effects of the PARP inhibitor Olaparib in cancer cells with normal homologous recombination repair (HR) such as MDA-MB-231, HeLa, and SKOV3. When used in combination with Olaparib, BER-IN-1 can induce S-phase arrest and apoptosis. This compound is utilized in research on cancers, including breast, cervical, and ovarian cancers.

BER-IN-1 (Compound BA-6) exhibits an IC50 of 10.92 μM against MDA-MB-231 cells, 6.37 μM against HeLa cells, 7.76 μM against SKOV3 cells, and 5.53 μM against OVCAR3 BRCA1−/− cells. When used in conjunction with Olaparib at concentrations of 0.7-50 μM over 24-72 hours, BER-IN-1 significantly reduces the viability of MDA-MB-231, HeLa, and OVCAR3 BRCA1−/− cells. At concentrations of 5-10 μM, BER-IN-1 combined with Olaparib inhibits colony formation in MDA-MB-231 and HeLa cancer cells. Additionally, at 5-50 μM, the combination leads to an increase in significant β-elimination products and induces DNA double-strand breaks in these cancer cells. Furthermore, administering BER-IN-1 at 5-10 μM for 24 hours with Olaparib induces S-phase arrest and apoptosis in MDA-MB-231 and HeLa cancer cells.