Rucaparib Camsylate

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Rucaparib Camsylate 是一种 PARP 抑制剂（PARP1，Ki 为 1.4 nM）。 Rucaparib Camsylate 还显示出与其他八个 PARP 结构域的结合亲和力。 Rucaparib 是酶测定中最有效的 PARP 抑制剂 (Ki: 1.4 nM)。在透化的 D283Med 细胞中，浓度为 1 μM 的 Rucaparib 可抑制 PARP-1 活性 97.1%。

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.

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.

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.

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Cell Cycle/DNA Damage

PARP

PARP1

Cancer

Metastatic Castration Resistant Prostate Cancer

1859053-21-6

555.66

C29H34FN3O5S

>98% (HPLC)

DMSO:82.33 mg/mL(148.17 mM)

CC1(C)[C@@H]2CC[C@@]1(CS(O)(=O)=O)C(=O)C2.CNCc1ccc(cc1)-c1[nH]c2cc(F)cc3C(=O)NCCc1c23

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(-20℃)

With Ice Pack

≥ 2 years