product name Rucaparib (AG-014699)
Description: Rucaparib, also known as AG-014699 or PF-01367338, is an inhibitor of PARP with Ki of 1.4 nM for PARP1 in a cell-free assay, it also shows binding affinity to eight other PARP domains. Rucaparib selectively binds to PARP1 and inhibits PARP1-mediated DNA repair, thereby enhancing the accumulation of DNA strand breaks and promoting genomic instability and apoptosis. This may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapy and radiation therapy.
References: Mol Cancer Ther. 2007 Mar;6(3):945-56; Br J Cancer. 2010 Nov 9;103(10):1588-96.
421.36
Formula
C19H18FN3O.H3PO4
CAS No.
459868-92-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 84 mg/mL (199.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms
AG-014699,PF-01367338
other peoduct :
| In Vitro |
In vitro activity: Rucaparib is a potent inhibitor of purified full-length human PARP-1 and shows higher inhibition of cellular PARP in LoVo and SW620 cells. Besides, Rucaparib binds detectably to eight other PARP domains, including PARP2, 3, 4, 10, 15, 16, TNKS1 and TNKS2. The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib could target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells. Kinase Assay: Inhibition of human full-length recombinant PARP-1 by [32P]NAD+ incorporation is measured. The [32P]ADP-ribose incorporated into acid insoluble material is quantified using a PhosphorImager. Ki is calculated by nonlinear regression analysis. Cell Assay: In the MDCKII parental cell line, which overexpressed human (h) ABCB1, both apically and basolaterally directed translocation of rucaparib were the same. Treatment of the cells with the ABCB1 inhibitor zosuquidar resulted in a slight decrease in apically directed transport, which could be either due to a specific inhibition of an unidentified rucaparib uptake transporter at the basolateral side, or inhibition of endogenous canine ABCB1. The result shown that rucaparib is a transported substrate of ABCB1. |
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| In Vivo | Rucaparib is not toxic but significantly enhances temozolomide-induced TGD in the DNA repair protein-competent D384Med xenografts. Pharmacokinetics studies also show that Rucaparib is detected in the brain tissue, which indicates that Rucaparib has potential in intra-cranial malignancy therapy. Rucaparib significantly potentiates the cytotoxicity of topotecan and temozolomide in NB-1691, SH-SY-5Y, and SKNBE (2c) cells. Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts. |
| Animal model | CD-1 nude mice bearing established D283Med xenografts |
| Formulation & Dosage | Dissolved in saline; 1 mg/kg; One or four daily by i.p. |
| References | Mol Cancer Ther. 2007 Mar;6(3):945-56; Br J Cancer. 2010 Nov 9;103(10):1588-96; Clin Cancer Res. 2009 Feb 15;15(4):1241-9. |
