Rucaparib phosphate

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。

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. (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.

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.

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. 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.

AG014699 phosphate | PF01367338 phosphate | AG 014699 phosphate

Cell Cycle/DNA Damage

PARP

PARP

Cancer

Ovarian Cancer

459868-92-9

421.3593

C19H21FN3O5P

>98% (HPLC)

DMSO: ≥ 33 mg/mL

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|

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

(-20℃)

With Ice Pack

≥ 2 years