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Rucaparib Phosphate
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Rucaparib Phosphate图片
CAS NO:459868-92-9
包装与价格:
包装价格(元)
2 mg电议
5 mg电议
10 mg电议
50 mg电议
100 mg电议
200 mg电议
1 mL*10 mM(in DMSO)电议

产品名称
PF-01367338 phosphate
AG-014699
PF-01367338
芦卡帕利
AG-014699 phosphate
瑞卡帕布磷酸盐
产品介绍
Rucaparib phosphate 是一种口服有效的PARP蛋白抑制剂,对 PARP-1 的Ki为 1.4 nM。它是六磷酸己糖脱氢酶 (H6PD) 抑制剂,有用于去势抵抗性前列腺癌 (CRPC) 的研究潜力。

产品描述

Rucaparib is an inhibitor of PARP (Ki: 1.4 nM for PARP1) that is used in clinical therapy to sensitize cancer cells to chemotherapy.

体外活性

AG14447 (the phosphate salt of Rucaparib) is the most potent PARP inhibitor in enzyme assays (Ki: 1.4 nmol/L) [1]. In permeabilised D283Med cells, Rucaparib (AG-014699), at concentrations of 0.1, 0.4 and 1?μ inhibited PARP-1 activity by 81.1, 96.8 and 97.1%, respectively [2]. AG014699 (≤10 μM) was cytotoxic to cells with mutated BRCA1/2 or XRCC3 and to UACC3199 cells with epigenetically silenced BRCA1 but not to cells without BRCA1/2 or XRCC3 mutations or that were heterozygous for BRCA2 mutation [3].

体内活性

When 10 mg/kg AG14447 was administered in combination with temozolomide, body weight loss was observed at days 4 to 13 posttreatment with the nadir body weight ranging from 83% to 96% of the starting weight. At a dose of 1 mg/kg, AG14447 also significantly increased temozolomide-induced body weight loss [1]. At 1?mg/kg daily five times, AG-014699 alone did not cause any marked toxicity or affect tumour growth compared with vehicle-only controls. Co-administration of AG-014699 with temozolomide also resulted in complete tumour regressions in all mice, of which three out of five were sustained throughout the experiment. The MMR-defective D283Med xenografts grew very rapidly and showed very little response to temozolomide alone (TGD of only 2 days) with no regressions observed in any mice [2].

激酶实验

We measured inhibition of human full-length recombinant PARP-1 by [32P]NAD+ incorporation as described previously. The [32P]ADP-ribose incorporated into acid insoluble material was quantified using a PhosphorImager. Kis were calculated by nonlinear regression analysis [1].

细胞实验

Inhibition of PARP activity in 5000 exponentially growing D283Med cells was measured following treatment with a range of AG-014699 concentrations (0–1?μ), in comparison with DMSO-only controls. Maximally stimulated PARP activity was measured in replicate samples (n?3) of permeabilised cells by immunological detection of the amount of poly(ADP-ribose) (PAR) formed, using 10H anti-PAR antibody, during a 6-min incubation with NAD+ and oligonucleotide (substrate and activator) by reference to a PAR standard curve using a GCLP-validated assay described previously [2].

动物实验

One or four daily doses of PARP inhibitor AG-014699 (1?mg/kg intraperitoneally (i.p.)) were given to CD-1 nude mice bearing established D283Med xenografts. At 0.5, 2, 6 and 24?h after the initial or fourth daily dose of AG-014699, three animals per time point were bled by cardiac puncture under general anaesthesia, and then killed. Plasma was separated from the blood samples using standard methods and stored at ?80°C. The brains and tumours were removed, snap frozen in liquid nitrogen and stored at ?80°C before analysis. Blood, tumour and brain tissue were removed from three untreated control animals and processed in the same way [2].

Cas No.

459868-92-9

分子式

C19H18FN3O·H3PO4

分子量

421.36

别名

PF-01367338 phosphate;AG-014699;PF-01367338;芦卡帕利;AG-014699 phosphate;瑞卡帕布磷酸盐

储存和溶解度

Ethanol:<1 mgml
H2O:<1 mgml
DMSO:78 mg/mL (185.1 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years