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编 号：F455154
分子式：C19H19ClFN3O
分子量：359.83
分子式：C19H19ClFN3O
分子量：359.83
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CAS No: 773059-19-1
产品详情
生物活性：
Rucaparib (AG014699) hydrochloride is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a Ki of 1.4 nM for PARP1. Rucaparib hydrochloride is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib hydrochloride has the potential for castration-resistant prostate cancer (CRPC) research.
体内研究：
Rucaparib (AG014699) hydrochloride and AG14584 significantly increase Temozolomide toxicity. Rucaparib (1 mg/kg) hydrochloride significantly increases Temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) hydrochloride 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) hydrochloride 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) hydrochloride has greatest antitumor effect with three complete regressions. Rucaparib (1 mg/kg; i.p.; daily for 5d) hydrochloride enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts.Animal Model:Female athymic nude mice, implanted SW620 colorectal tumor cells (1 × 107 cells per animal) s.c.
Dosage:0.1 mg/kg in combination with Temozolomide (p.o., 200 mg/kg), 0.05, 0.15, and 0.5 mg/kg in combination with Temozolomide (p.o., 68 mg/kg) or 10 mg/kg
Administration:IP, single dose for 0.1 mg/kg and 10 mg/kg, five daily doses for 0-0.5 mg/kg
Result:Significantly increased Temozolomide toxicity, showed outstanding chemosensitization potency and caused enhancement of Temozolomide-induced tumor growth delay.
Animal Model:CD-1 nude mice bearing established Capan-1 xenografts
Dosage:10 mg/kg or 50, 100 and 150?mg/kg
Administration:IP for 10 mg/kg; PO for 50, 100 and 150?mg/kg, single dose (Pharmacokinetics)
Result:Parent drug was detectable in the plasma only at 30?min after 10?mg/kg i.p and up to 4?h for 50–150?mg/kg p.o.. Was still detectable in most mice receiving oral rucaparib at 3 days. Does not easily cross the plasma membrane.
Animal Model:CD-1 nude mice bearing established Capan-1 xenografts
Dosage:10?mg/kg i.p. daily for 5 days per week for 6 weeks, 50 or 150?mg/kg p.o. daily × five weekly × six, 150?mg/kg p.o. once per week for 6 weeks or three times per week for 6 weeks, or 150?mg/kg p.o. daily for five days every 3 weeks
Administration:IP or PO
Result:10?mg/kg i.p. significantly inhibited the growth of the tumor, daily oral administration at 150?mg/kg had an equivalent effect on tumor growth to 10?mg/kg i.p.. The schedule with the greatest antitumor effect was oral administration of 150?mg/kg on a once weekly schedule with three complete regressions.
Animal Model:CD-1 nude mice, NB1691 and SHSY5Y xenografts
Dosage:1 mg/kg
Administration:IP, daily for 5 d in combination with Temozolomide (orally daily ×5 at a dose of 68 mg/kg)
Result:Enhanced the antitumor activity of Temozolomide and indicated complete and sustained tumor regression.
体外研究：
Rucaparib (AG014699) hydrochloride is a possible N-demethylation metabolite of AG14644. Rucaparib (0.1, 1, 10, 100 μM; 24 hours) hydrochloride 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 hydrochloride is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib hydrochloride can target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. Rucaparib hydrochloride inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells.
Rucaparib (AG014699) hydrochloride is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a Ki of 1.4 nM for PARP1. Rucaparib hydrochloride is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib hydrochloride has the potential for castration-resistant prostate cancer (CRPC) research.
体内研究：
Rucaparib (AG014699) hydrochloride and AG14584 significantly increase Temozolomide toxicity. Rucaparib (1 mg/kg) hydrochloride significantly increases Temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) hydrochloride 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) hydrochloride 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) hydrochloride has greatest antitumor effect with three complete regressions. Rucaparib (1 mg/kg; i.p.; daily for 5d) hydrochloride enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts.Animal Model:Female athymic nude mice, implanted SW620 colorectal tumor cells (1 × 107 cells per animal) s.c.
Dosage:0.1 mg/kg in combination with Temozolomide (p.o., 200 mg/kg), 0.05, 0.15, and 0.5 mg/kg in combination with Temozolomide (p.o., 68 mg/kg) or 10 mg/kg
Administration:IP, single dose for 0.1 mg/kg and 10 mg/kg, five daily doses for 0-0.5 mg/kg
Result:Significantly increased Temozolomide toxicity, showed outstanding chemosensitization potency and caused enhancement of Temozolomide-induced tumor growth delay.
Animal Model:CD-1 nude mice bearing established Capan-1 xenografts
Dosage:10 mg/kg or 50, 100 and 150?mg/kg
Administration:IP for 10 mg/kg; PO for 50, 100 and 150?mg/kg, single dose (Pharmacokinetics)
Result:Parent drug was detectable in the plasma only at 30?min after 10?mg/kg i.p and up to 4?h for 50–150?mg/kg p.o.. Was still detectable in most mice receiving oral rucaparib at 3 days. Does not easily cross the plasma membrane.
Animal Model:CD-1 nude mice bearing established Capan-1 xenografts
Dosage:10?mg/kg i.p. daily for 5 days per week for 6 weeks, 50 or 150?mg/kg p.o. daily × five weekly × six, 150?mg/kg p.o. once per week for 6 weeks or three times per week for 6 weeks, or 150?mg/kg p.o. daily for five days every 3 weeks
Administration:IP or PO
Result:10?mg/kg i.p. significantly inhibited the growth of the tumor, daily oral administration at 150?mg/kg had an equivalent effect on tumor growth to 10?mg/kg i.p.. The schedule with the greatest antitumor effect was oral administration of 150?mg/kg on a once weekly schedule with three complete regressions.
Animal Model:CD-1 nude mice, NB1691 and SHSY5Y xenografts
Dosage:1 mg/kg
Administration:IP, daily for 5 d in combination with Temozolomide (orally daily ×5 at a dose of 68 mg/kg)
Result:Enhanced the antitumor activity of Temozolomide and indicated complete and sustained tumor regression.
体外研究：
Rucaparib (AG014699) hydrochloride is a possible N-demethylation metabolite of AG14644. Rucaparib (0.1, 1, 10, 100 μM; 24 hours) hydrochloride 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 hydrochloride is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib hydrochloride can target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. Rucaparib hydrochloride inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells.
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