Description
Rucaparib (AG-014699, PF-01367338) can inhibit PARP with IC50 of 1.4 nM.
Storage
2 years at -20centigrade Powder
Molecular Formula
C19H18FN3O.H3PO4
Chemical Name
8-fluoro-5-(4-((methylamino)methyl)phenyl)-3,4-dihydro-2H-azepino[5,4,3-cd]indol-1(6H)-one phosphoric acid
Solubility
DMSO 84 mg/mL Water
In vitro
Rucaparib (AG-014699, PF-01367338) is a potent inhibitor of purified full-length human PARP-1. AG-014699, at concentrations of 0.1, 0.4 and 1 mM, inhibited PARP-1 activity by 81.1, 96.8 and 97.1%, respectively. At the concentration of 0.4 mM, AG-014699 caused almost total inhibition of the PARP activity in medulloblastoma cells. AG014699, at the concentration less than 10 uM, was cytotoxic to cells with mutated BRCA1/2 or XRCC3 and to UACC3199 cells with epigenetically silenced BRCA1. AG014699 induced DNA double-strand breaks in all nine cell lines studied. HRR was observed only in cells with functional BRCA1/2 proteins.
In vivo
(1)Combination of AG-014699 and temozolomide can produce a increase in temozolomide-induced tumour growth delay in D384Med xenografts. Consistent with the in vitro data, temozolomide caused complete tumour regressions of D425Med xenografts, whereas D283Med xenografts were relatively resistant. AG-014699 was not toxic, accumulated and reduced PARP activity with more than 75% in xenograft and brain tissues. (2) Combination of AG-014699 and carboplatin can reduce growth of xenograft tumors with BRCA1/2 mutations or with epigenetically silenced BRCA1.
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