Rucaparib phosphate

SKU: orb1225017

Description

An inhibitor of PARP with Ki of 1.4 nM for PARP1 in a cell-free assay, also showing binding affinity to eight other PARP domains; inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells; enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts.Ovarian Cancer Approved(In Vitro):Rucaparib (AG014699) phosphate is a possible N-demethylation metabolite of AG14644.Rucaparib (0.1, 1, 10, 100 μM; 24 hours) phosphate is cytotoxic and has the LC50 being 5 μM in Capan-1 (BRCA2 mutant) cells and only 100 nM in MX-1 (BRCA1 mutant) cells.The radio-sensitization by Rucaparib phosphate is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib phosphate can target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions.Rucaparib phosphate inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells.\n(In Vivo):Rucaparib (AG014699) phosphate and AG14584 significantly increase Temozolomide toxicity. Rucaparib (1 mg/kg) phosphate significantly increases Temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) phosphate results in a 50% increase in the temozolomide-induced tumor growth delay.Rucaparib (10 mg/kg for i.p. or 50, 150 mg/kg for p.o.; daily for 5 days per week for 6 weeks) phosphate significantly inhibits the growth of the tumor, and there is one complete tumor regression and two persistent partial regressions.Rucaparib (150 mg/kg; p.o.; once per week for 6 weeks or three times per week for 6 weeks) phosphate has greatest antitumor effect with three complete regressions.Rucaparib phosphate enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 459868-92-9
• MW: 421.3593
• Purity: >98% (HPLC)
• Formula: C₁₉H₂₁FN₃O₅P
• SMILES: OP(O)(O)=O.CNCC1=CC=C(C=C1)C1=C2CCNC(=O)C3=CC(F)=CC(N1)=C23 |c:9,11,14,24,t:7,21,28|
• Target: PARP
• Solubility: DMSO: ≥ 33 mg/mL

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AG014699 phosphate | PF01367338 phosphate | AG 014699 phosphate

Quick Database Links

Gene Symbol

PARP