生物活性分子抑制剂AG14361

生物活性分子抑制剂 特异性抑制剂 激动剂 化合物库 重组蛋白 AG14361  纯度: 99.06%

AG14361 是一种有效的 PARP-1 抑制剂,Ki 值 < 5 nM,在通透的 SW620 细胞和完整的 SW620 细胞中,抑制 PARP-1 的活性,IC50 值分别为 29 nM 和 14 nM。

AG14361

AG14361 Chemical Structure

CAS No. : 328543-09-5

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥1392 In-stock
5 mg ¥1265 In-stock
10 mg ¥2380 In-stock
50 mg ¥7217 In-stock
100 mg ¥12425 In-stock
200 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

AG14361 相关产品

相关化合物库:

  • Bioactive Compound Library Plus
  • Cell Cycle/DNA Damage Compound Library
  • Epigenetics Compound Library
  • Anti-Cancer Compound Library
  • Anti-Aging Compound Library
  • Anti-Breast Cancer Compound Library
  • Anti-Pancreatic Cancer Compound Library

生物活性

AG14361 is a potent PARP-1 inhibitor, with a Ki of < 5 nM, and in permeabilized SW620 and intact SW620 cells, the IC50s are 29 nM and 14 nM, respectively.

IC50 & Target[1]

PARP-1

0.5 nM (Ki)

体外研究
(In Vitro)

AG14361 is a potent PARP-1 inhibitor, with a Ki of < 5 nM, and in permeabilized SW620 and intact SW620 cells, the IC50s are 29 nM and 14 nM, respectively. AG14361 inhibits the proliferation of human cancer cells, such as A549, LoVo, and SW620 cells, with GI50s of 14 μM, 11.2 μM and 20 μM, respectively. Furthermore, AG14361 in combination with NSC 362856 markedly reduces the GI50 value of NSC 362856 in LoVo and A549 cells, but does not exert such an effect in SW620 cells[1]. AG14361 suppresses breast cancer cells with IC50s of 17 μM and 25 μM for 92 J-wt-BRCA1 and 92 J-sh-BRCA1 cells, respectively. AG14361 induces caspase 3/7 activation and cell cycle abnormalities, and also inhibits NF-κB signaling[2]. AG14361 (0.4 μM) enhances the growth-inhibitory and cytotoxic effects of topoisomerase I poisons, with no obvious effect on the formation and reversal of cleavable complexes, and increases the persistence of camptothecin-induced DNA single-strand breaks[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

AG14361 (5 and 15 mg/kg, i.p.) has no toxicity and does not inhibit the growth of tumor. However, AG14361 markedly enhances NSC 362856 activity against LoVo xenografts and delays tumor growth when combined with NSC 362856. AG14361 (15 mg/kg, i.p.) treatment before irradiation dramaticly increases the sensitivity to radiation therapy of mice bearing LoVo xenografts[1]. AG14361 (30 mg/kg) synergizes lestaurtinib activity on inhibiting breast cancer tumors in allografts[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

分子量

320.39

Formula

C19H20N4O

CAS 号

328543-09-5

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 83.33 mg/mL (260.09 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 3.1212 mL 15.6060 mL 31.2120 mL
5 mM 0.6242 mL 3.1212 mL 6.2424 mL
10 mM 0.3121 mL 1.5606 mL 3.1212 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。-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

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.08 mg/mL (6.49 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (6.49 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 20.8 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。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.08 mg/mL (6.49 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (6.49 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 20.8 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。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 3.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 2.08 mg/mL (6.49 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (6.49 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Calabrese CR, et al. Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst. 2004 Jan 7;96(1):56-67.

    [2]. Vazquez-Ortiz G, et al. Drug repurposing screen identifies lestaurtinib amplifies the ability of the poly (ADP-ribose) polymerase 1 inhibitor AG14361 to kill breast cancer associated gene-1 mutant and wild type breast cancer cells. Breast Cancer Res. 2014 Jun 24;16(3):R67.

    [3]. Smith LM, et al. The novel poly(ADP-Ribose) polymerase inhibitor, AG14361, sensitizes cells to topoisomerase I poisons by increasing the persistence of DNA strand breaks. Clin Cancer Res. 2005 Dec 1;11(23):8449-57.

Kinase Assay
[1]

The activity of full-length recombinant human PARP-1 is measured in a reaction mixture containing 20 nM PARP-1, 500 μM NAD+ plus [32P]NAD+ (0.1-0.3 μCi per reaction mixture), and activated calf thymus DNA (10 μg/mL) at 25°C; the reaction is terminated after 4 minutes by adding ice-cold 10% (wt/vol) trichloroacetic acid. The reaction product [32P]ADP-ribose incorporated into acid-insoluble material is deposited onto Whatman GF/C glass fiber filters with a microfiltration apparatus and quantified with a PhosphorImager. Inhibition of PARP-1 activity by AG14361 at 0-600 nM is measured, and the Ki for AG14361 is calculated by nonlinear regression analysis[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

Cell viability assay is performed using a luciferase-coupled ATP quantization assay of metabolically active cells in a 96-well plate and MTT. For MTT, 1 to 2 × 104 cells are plated per one well of a 24-well plate. Target drugs (AG14361) at various concentrations are dissolved in DMSO and then added to the cells in 10% fetal bovine serum-containing Dulbecco’s modified Eagle’s medium (DMEM), IC50 concentration of AG14361 are also added to each well. The final DMSO concentration is kept at 0.1% after the addition to medium. After 48 hr medium is removed and 0.3 mL of 0.1% MTT in phosphate-buffered saline (PBS) is added in each well. After incubation for 30 min in a 37°C CO2 incubator, MTT solution is removed and 0.8 mL of 2-propanol is added. After shaking for 30 min, OD560 is measured using a plate reader. Plating for each time point is done in triplicate[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

CD-1 nude mice bearing palpable, subcutaneous SW620 or LoVo xenografts are treated intraperitoneally with normal saline (control animals) or AG14361 (at 5 or 15 mg/kg) alone daily for 5 days (five mice per group). For drug combinations, AG14361 is administered intraperitoneally daily for 5 days immediately before administering the cytotoxic drug (NSC 362856 at 68 mg/kg orally or CPT-11 at 2.5 mg/kg intraperitoneally) or 30 minutes before applying 2 Gy of x-irradiation locally to the tumor daily for 5 days. Tumor volumes, determined from two-dimensional caliper measurements and the equation a2 × b/2 (where a is the width and b is the length of the tumor), are presented as median relative tumor volume (RTV). That is, RTV1 is the tumor volume on the initial day of treatment (day 0), and RTV4 is the tumor volume 4 times that on the initial day of treatment. Tumor growth delay is defined as the time to RTV4 in drug-treated or irradiated mice compared with the time to RTV4 in control (vehicle alone) mice[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Calabrese CR, et al. Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst. 2004 Jan 7;96(1):56-67.

    [2]. Vazquez-Ortiz G, et al. Drug repurposing screen identifies lestaurtinib amplifies the ability of the poly (ADP-ribose) polymerase 1 inhibitor AG14361 to kill breast cancer associated gene-1 mutant and wild type breast cancer cells. Breast Cancer Res. 2014 Jun 24;16(3):R67.

    [3]. Smith LM, et al. The novel poly(ADP-Ribose) polymerase inhibitor, AG14361, sensitizes cells to topoisomerase I poisons by increasing the persistence of DNA strand breaks. Clin Cancer Res. 2005 Dec 1;11(23):8449-57.

所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务