Stemcell, 100-1168, Rucaparib

Inhibit cancer cells growth with rucaparib, a poly ADP ribose polymerase (PARP) inhibitor (PARP1 Ki < 5 nM; Thomas et al.). Highly potent and cell-permeable, rucaparib inhibits PARP in cancer cells with BRCA1 or BRCA2 mutations (Musella et al.). Activated by DNA breaks, PARP promotes repair of DNA damage through the relaxation of chromatin and recruitment of other repair proteins. Rucaparib inhibits this activity, which leads to DNA damage and death of cancer cells (Javle & Curtin ). In addition to PARP1, rucaparib also inhibits PARP2, 3, 4, 12, 15, and 16, as well as tankyrase 1 and 2 (Musella et al.).



Rucaparib has been used for:



CANCER RESEARCH

· Antagonizes multidrug resistance (MDR) in doxorubicin and paclitaxel resistance cervical cancer cell lines by binding to the active site of ATP-binding cassette (ABC) transporters (Chen et al.).

· Cytotoxic to human cell lines with mutated BRCA1/2 (MDA-MB-436, HCC1937 and CAPAN-1) and to UACC3199 cells with epigenetically silenced BRCA1 but not to cell lines without BRCA1/2 mutations (MCF7, MDA-MB-231, HCC1937-BRCA1 and OSEC-2) or heterozygous for BRCA2 mutation (OSEC-1) (Drewet al.).

· Reduces growth of mouse xenograft tumors with BRCA1/2 mutations or with epigenetically silenced BRCA1 (Drew et al.).

· Concentration-dependent antiproliferative effects in many ovarian cancer cell lines with and without BRCA1/2 mutations (Ihnen et al.).