Rucaparib

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

一种 PARP 抑制剂，在无细胞测定中对 PARP1 的 Ki 为 1.4 nM，还显示出与其他八个 PARP 结构域的结合亲和力。

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) is a possible N-demethylation metabolite of AG14644.Rucaparib (0.1, 1, 10, 100 μM; 24 hours) 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 is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib can 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.(In Vivo):Rucaparib (AG014699) and AG14584 significantly increase Temozolomide toxicity. 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.Rucaparib (10?mg/kg for i.p. or 50, 150 mg/kg for p.o.; daily for 5 days per week for 6 weeks) 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) has greatest antitumor effect with three complete regressions.Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts.

Rucaparib (AG014699) is a possible N-demethylation metabolite of AG14644. Rucaparib (0.1, 1, 10, 100 μM; 24 hours) 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 is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib can 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.

Rucaparib (AG014699) and AG14584 significantly increase Temozolomide toxicity. 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. Rucaparib (10?mg/kg for i.p. or 50, 150 mg/kg for p.o.; daily for 5 days per week for 6 weeks) 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) has greatest antitumor effect with three complete regressions. Rucaparib 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 for i.p. or 50, 150 mg/kg for p.o.Administration:IP or PO Result:Significantly inhibited the growth of the tumor.

AG014699 | PF01367338 | AG 014699 | PF 01367338

Cell Cycle/DNA Damage

PARP

PARP1

Cancer

Ovarian Cancer

283173-50-2

323.3641

C19H18FN3O

>98% (HPLC)

10 mM in DMSO

CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=C3C(=CC(=C4)F)N2

6H-Pyrrolo[4,3,2-ef][2]benzazepin-6-one, 8-fluoro-1,3,4,5-tetrahydro-2-[4-[(methylamino)methyl]phenyl]-

(-20℃)

With Ice Pack

≥ 2 years