Table 1.

Summary of BMN 673 in vitro activities

PARP1 enzyme inhibitionIC50, nmol/LCellular PAR synthesisEC50, nmol/LCapan-1 cytotoxicityIC50, nmol/LTemozolomide potentiationGI50, nmol/L
Veliparib4.735.9>10,0006,203
Rucaparib1.984.7609144
Olaparib1.943.6259237
LT-006281.824.585
BMN 6730.572.553

NOTE: Activities of BMN 673, LT-00628, and three clinical PARP1/2 inhibitors veliparib, rucaparib, and olaparib were compared in four in vitro assays: (i) concentration for 50% inhibition in PARP1 enzyme assay (IC50); (ii) concentration for 50% inhibition in cellular PAR synthesis assay in LoVo cells (EC50); (iii) concentration for 50% Capan-1 cell survival reduction in single-agent cytotoxicity assay (IC50); and (iv) concentration that, when combined with 200 ╬╝mol/L of temozolomide, resulted in 50% growth inhibition of LoVo cells in temozolomide potentiation assay (GI50). Assay conditions are described in the Materials and Methods. Values are average data from three to four independent experiments.