Shen, Yuqiao, et al. Clinical Cancer Research, 2013, 19(18), 5003-5015.
Researchers tested BMN 673 (Talazoparib) to determine its anticancer potential by targeting tumor cells that lack proper DNA repair mechanisms. Researchers evaluated the potency and selectivity of the drug as both a standalone treatment and in combination with other anticancer drugs using in vitro and xenograft models.
Key Findings
BMN 673 demonstrated strong PARP1/2 inhibition with a PARP1 IC50 of 0.57 nmol/L while showing selective antitumor cytotoxicity and activation of DNA repair biomarkers at lower concentrations compared to previous PARP1/2 inhibitors. The compound demonstrated a 20- to 200-fold increase in effectiveness against tumor cells with BRCA1, BRCA2, or PTEN mutations when tested in vitro compared to other existing inhibitors.
High oral bioavailability of the compound exceeded 40% in rats when it was combined with carboxylmethyl cellulose. The compound effectively reduced tumor growth when administered orally to xenograft models containing BRCA mutations or PTEN deficiencies at doses that did not cause adverse effects. Combining BMN 673 with temozolomide, SN38, or platinum-based drugs produced synergistic or additive antitumor effects.
