| 产品介绍 |
Rucaparib (AG014699) phosphate 是一种口服有效的 PARP 蛋白 (PARP-1, PARP-2 and PARP-3) 抑制剂，对 PARP-1 的 Ki 为 1.4 nM。Rucaparib phosphate 是六磷酸己糖脱氢酶 (H6PD) 抑制剂。Rucaparib phosphate 具有用于去势抵抗性前列腺癌 (CRPC) 研究的潜力。
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| 生物活性 |
Rucaparib (AG014699) phosphate 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 phosphate is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib phosphate has the potential for castration-resistant prostate cancer (CRPC) research[4].
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| 体外研究 |
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[5].
Rucaparib phosphate inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells[6].
西域 has not independently confirmed the accuracy of these methods. They are for reference only. |
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| 体内研究 |
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[6].
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| 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[6] |
| 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. |
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| 体内研究 |
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[6].
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| 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[6] |
| 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. |
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| 性状 | Solid |
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| 溶解性数据 |
In Vitro:
DMSO : ≥ 33 mg/mL (78.32 mM)
H2O : 5 mg/mL (11.87 mM; ultrasonic and warming and heat to 60°C)
* "≥" means soluble, but saturation unknown.
配制储备液
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浓度
溶剂体积
质量
|
1 mg |
5 mg |
10 mg |
| 1 mM |
2.3733 mL |
11.8663 mL |
23.7327 mL |
| 5 mM |
0.4747 mL |
2.3733 mL |
4.7465 mL |
| 10 mM |
0.2373 mL |
1.1866 mL |
2.3733 mL |
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：
——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶
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1.
请依序添加每种溶剂： 5% DMSO 40% PEG300 5% Tween-80 50% saline Solubility: ≥ 2.5 mg/mL (5.93 mM); Clear solution
-
2.
请依序添加每种溶剂： 5% DMSO 95% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (5.93 mM); Clear solution
-
3.
请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline Solubility: ≥ 2.17 mg/mL (5.15 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (5.15 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
-
4.
请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline) Solubility: ≥ 2.17 mg/mL (5.15 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (5.15 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
-
5.
请依序添加每种溶剂： 10% DMSO 90% corn oil Solubility: ≥ 2.17 mg/mL (5.15 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (5.15 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
-
6.
请依序添加每种溶剂： 1% DMSO 99% saline Solubility: ≥ 0.5 mg/mL (1.19 mM); Clear solution
*以上所有助溶剂都可在 西域 网站选购。
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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| 储存方式 |
4°C, sealed storage, away from moisture
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| 参考文献 |
-
. Thomas HD, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther, 2007, 6(3), 945-956.
[Content Brief]
. J Murray, et al. Tumour cell retention of rucaparib, sustained PARP inhibition and efficacy of weekly as well as daily schedules. Br J Cancer. 2014 Apr 15;110(8):1977-84.
[Content Brief]
. Matt Shirley, et al. Rucaparib: A Review in Ovarian Cancer. Target Oncol. 2019 Apr;14(2):237-246.
[Content Brief]
[4]. Jianneng Li, et al. Hexose-6-phosphate dehydrogenase blockade reverses prostate cancer drug resistance in xenograft models by glucocorticoid inactivation. Sci Transl Med. 2021 May 26;13(595):eabe8226.
[Content Brief]
[5]. Hunter JE, et al. NF-κB mediates radio-sensitization by the PARP-1 inhibitor, AG-014699. Oncogene, 2012, 31(2), 251-264.
[Content Brief]
[6]. Daniel RA, et al. Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. Clin Cancer Res, 2009, 15(4), 1241-1249.
[Content Brief]
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1. 物质的识别
| 产品名： |
AG-014699 phosphate |
| CAS号： |
459868-92-9 |
| 制造商/供应商： |
西域试剂
网站：www.hzbp.cn 邮件：13911702513@139.com |
2. 合成/成分数据
| 产品名： |
AG-014699 phosphate |
| 别名： |
PF-01367338, Rucaparib phosphate |
| 分子式： |
C19H18FN3O.H3PO4 |
| 分子量： |
421.36 |
3. 急救措施
| 吸入后： |
如果吸入，移至空气新鲜处，如果呼吸困难，给输氧，如呼吸停止，给予人工呼吸。 |
| 皮肤接触后： |
用大量的水冲洗，移除污染的衣服和鞋子。 |
| 眼睛接触后： |
检查并取下隐形眼镜，并用大量的水冲洗；呼叫医生。 |
| 吞食后： |
如果吞食，用大量纯净水漱口；呼叫医生。 |
4. 消防措施
| 适当的灭火剂： |
雾状水，二氧化碳，干粉或泡沫。 |
| 防护设备： |
穿戴自给式呼吸器和防护服，以防止与皮肤和眼睛接触。 |
5. 泄漏应急处理
| 安全防范措施： |
封锁泄漏区域；穿戴自给式呼吸器，防护服和厚橡胶手套。 |
| 清洁/收集措施： |
使用液体粘合原料（硅藻土，通用粘合剂）吸取精细粉末；
使用酒精擦洗表面和设备除去污渍；
根据第11条处理被污染的材料。 |
6. 处理和储存
| 安全处理说明： |
避免吸入和接触皮肤，眼睛及衣物；材料可能略微具有刺激性。 |
| 储存： |
粉末型式 -20°C 3年；4°C 2年
溶于溶剂 -80°C 6个月；-20°C 1个月
|
7. 接触控制和个人防护
| 呼吸设备： |
NIOSH / MSHA认可的呼吸器。 |
| 双手保护： |
耐化学腐蚀的橡胶手套。 |
| 眼睛防护： |
化学安全护目镜。 |
8. 稳定性和反应活性
| 稳定性： |
按照说明存储是稳定的；避免强氧化剂。 |
| 热分解/其他要避免的情况： |
避免光和热。 |
9. 毒性资料
| 急性毒性： |
无可用资料。 |
| 主要刺激性影响： |
无可用资料。 |
| 在皮肤上： |
无可用资料。 |
| 对眼睛： |
无可用资料；可能具有刺激性。 |
10. 生态资料
11. 废弃处置
12. 运输信息
| 正确的运输名称： |
无 |
| 非危险品运输： |
这种物质被视为非危险品运输。 |
13. 法规信息
14. 其他信息
| 这种化学品仅供受过训练的，有经验的研究人员在穿戴适当装备和授权允许的情况下进行操作处理。以上信息基于我们目前的知识被认为是正确的，但只适用于作为有经验人员的指导。请咨询您自己的安全顾问，并遵守当地和国家的安全法规。在任何其他没有被警告的情况下，并不意味着绝对没有危险存在。西域生物技术不承担任何使用这种化学品所造成的损害和责任。2023 西域生物技术版权所有。 |
[1]. Thomas HD, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther, 2007, 6(3), 945-956.
[2]. Hunter JE, et al. NF-κB mediates radio-sensitization by the PARP-1 inhibitor, AG-014699. Oncogene, 2012, 31(2), 251-264.
[3]. Daniel RA, et al. Central nervous system penetration and enhancement of temozolomide activity in childhood medulloblastoma models by poly(ADP-ribose) polymerase inhibitor AG-014699. Br J Cancer, 2010, 103(10), 1588-1596.
[4]. Daniel RA, et al. Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. Clin Cancer Res, 2009, 15(4), 1241-1249.
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