AZD2461

AZD2461 is a novel PARP inhibitor with low affinity for Pgp than Olaparib. AZD2461 has an 80-fold increased Mdr1b expression on Olaparib-resistant KB1P tumor T6-28, without inhibition of Pgp. AZD2461 induces loss of 53BP1 expression in mice with KB1P tumors with short-term treatment. Long-term AZD2461 treatment is well tolerated and doubled the median relapse-free survival. Importantly, PARPi resistance was minimized by long-term treatment with the novel PARP inhibitor AZD2461, which is a poor P-glycoprotein substrate.