Olaparib

A highly potent and selective PARP-inhibitor with IC₅₀ values of 5 nM and 1 nM for PARP-1 and PARP-2, respectively [1]. In a genetically engineered mouse model for BRCA1-associated breast cancer olaparib inhibited tumor growth and improved survival with no signs of toxicity [2]. Synergizes with many other anticancer agents [3]. Shows efficacy in colorectal cancers [4]. Prevents house dust mite allergen-induced asthma in a mouse model [5].

References:

1) Menear et al. (2008), 4-[3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose)polymerase-1;  J.Med.Chem. 51 6581

2) Rottenberg et al. (2008), High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs; Proc.Natl.Acad.Sci.USA 105 17079

3) Avila-Arroyo et al. (2015), Synergistic effect of Trabectedin and Olaparib combination regimen in breast cancer cell lines; J.Breast Cancer 18 329

4) Xu et al. (2015), Combined olaparib and oxaliplatin inhibits tumor proliferation and induces G2/M arrest and γ-H2AX foci formation in colorectal cancer; Onco.Targets Ther. 8 3047

5) Ghonim et al. (2015), PARP is activated in human asthma and its inhibition by olaparib blocks house dust mite-induced disease in mice; Clin.Sci.(Lond) 129 951