Background:

BMN673 is a potent and selective PARP1/2 inhibitor with Ki of 1.2 and 0.9 nM, respectively¹. It had no effect on panels of 72 receptors, ion channels, and enzymes¹. BMN673 showed IC50 value of 0.57 nM in enzymatic assay of PARP1¹. In in vitro assay, it exhibited greater potency than other existing PARP inhibitors, such as veliparib, rucaparib, and olaparib². It is also much more potent at trapping PARP-DNA complexes than other PARP inhibitors³.

BMN673 has shown anti-tumor activity both in vitro and in vivo. It inhibited proliferation of tumor cells and xenografts with defects in homologous recombination¹. The combination of BMN673 and DNA-damaging agents demonstrated synergistic anti-tumor effects¹. In addition, study showed that the expression levels of DNA repair proteins and status of PI3K pathway predict response to BMN673 in small cell lung cancer⁴.

BMN673 is currently under investigation in multiple clinical trials for advanced solid tumors or hematological malignancies, either as monotherapy or in combination with other anti-tumor agents.

参考文献:
1. Shen Y, Rehman FL, Feng Y et al. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin Cancer Res 2013; 19: 5003-5015.
2. Cardnell RJ, Byers LA. Proteomic Markers of DNA Repair and PI3K Pathway Activation Predict Response to the PARP Inhibitor BMN 673 in Small Cell Lung Cancer--Response. Clin Cancer Res 2014; 20: 2237.
3. Murai J, Huang SY, Renaud A et al. Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther 2014; 13: 433-443.
4. Cardnell RJ, Feng Y, Diao L et al. Proteomic markers of DNA repair and PI3K pathway activation predict response to the PARP inhibitor BMN 673 in small cell lung cancer. Clin Cancer Res 2013; 19: 6322-6328.