Rucaparib Camsylate

SKU: orb1219513

Description

Rucaparib Camsylate is a PARP inhibitor (PARP1,Ki of 1.4 nM). Rucaparib Camsylate also displays binding affinity to eight other PARP domains. Rucaparib is the most effective PARP inhibitor in enzyme assays (Ki: 1.4 nM). Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilized D283Med cells. Rucaparib could target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-κB and is independent of SSB repair inhibition.Rucaparib is not toxic but obviously enhances temozolomide-induced TGD in the DNA repair protein-competent D384Med xenografts. Rucaparib and AG14584 obviously (P < 0.05) increase temozolomide toxicity. Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts. Rucaparib significantly potentiates the cytotoxicity of topotecan and temozolomide in NB-1691, SH-SY-5Y, and SKNBE (2c) cells. Rucaparib (1 mg/kg) significantly increases temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) results in a 50% increase in the temozolomide-induced tumor growth delay. Pharmacokinetics studies also show that Rucaparib is detected in the brain tissue, which indicates that Rucaparib has potential in intra-cranial malignancy therapy.

Key Properties

• CAS Number: 1859053-21-6
• MW: 555.66
• Purity: >98% (HPLC)
• Formula: C₂₉H₃₄FN₃O₅S
• SMILES: CC1(C)[C@@H]2CC[C@@]1(CS(O)(=O)=O)C(=O)C2.CNCc1ccc(cc1)-c1[nH]c2cc(F)cc3C(=O)NCCc1c23
• Target: PARP
• Solubility: DMSO:82.33 mg/mL(148.17 mM)

Bioactivity

• In Vivo:
  Rucaparib (AG014699) monocamsylate and AG14584 significantly increase Temozolomide toxicity. Rucaparib (1 mg/kg) monocamsylate significantly increases Temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) monocamsylate 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) monocamsylate 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) monocamsylate has greatest antitumor effect with three complete regressions. Rucaparib monocamsylate enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts. Animal model: Female CD-1 nude mice aged 10-12 weeks with Capan-1 cells. Dosage: 10 mg/kg or 50, 150 mg/kg. Administration: 10 mg/kg for i.p. or 50, 150 mg/kg for p.o. Result: Significantly inhibited the growth of the tumor.
• In Vitro:
  Rucaparib (AG014699) monocamsylate is a possible N-demethylation metabolite of AG14644. Rucaparib (0.1, 1, 10, 100 μM; 24 hours) monocamsylate 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 monocamsylate is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib monocamsylate can target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. Rucaparib monocamsylate inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells.

Storage & Handling

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

Quick Database Links

Gene Symbol

PARP