ART558 是一种纳摩尔、高效、有选择性、低分子量、变构 DNA 聚合酶活性的Polθ抑制剂(IC50=7.9 nM)。ART558 可用于癌症研究。
| 生物活性 | ART558 is a nanomolar potent, selective, low molecular weight, allosteric DNA polymerase activity ofPolθinhibitor (IC50=7.9 nM). ART558 can be used for the research ofcancer[1]. |
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体外研究
(In Vitro) | ART558 (0~10 μM; 7 days; BRCA2wild-typeor BRCA2-/-cells) shows synthetic lethality and a combinatorial effect with the PARPi olaparib in previously described isogenic models of BRCA1-deficiency[1].
ART558 (5μM; 0~72 hours; BRCA2wild-typeor BRCA2-/-cells) shows γH2AX accumulation in cells[1].
ART558 inhibits the major Polθ mediated DNA repair process, Theta-Mediated End Joining, without targeting NonHomologous End Joining. ART558 elicits DNA damage and synthetic lethality in BRCA1- or BRCA2-mutant tumour cells and enhances the effects of a PARP inhibitor.
ART558 increases biomarkers of single-stranded DNA and synthetic lethality in 53BP1-defective cells whilst the inhibition of DNA nucleases that promote end-resection reversed these effects, implicating these in the synthetic lethal mechanism-of-action. ART558 increases the residence time of YFP-tagged full-length Polθ at sites of laserinduced DNA damage[1].
Cell Viability Assay[1] | Cell Line: | BRCA2wild-typeor BRCA2-/-cells | | Concentration: | 0~10 μM | | Incubation Time: | 7 days | | Result: | Showed synthetic lethality and a combinatorial effect with the PARPi olaparib in previously described isogenic models of BRCA1-deficiency. |
Western Blot Analysis[1] | Cell Line: | BRCA2wild-typeor BRCA2-/-cells | | Concentration: | 5μM | | Incubation Time: | 0~72 hours | | Result: | Showed γH2AX accumulation in cells. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture and light *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light) |
| 溶解性数据 | In Vitro: DMSO : 170 mg/mL(406.30 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.3900 mL | 11.9500 mL | 23.9000 mL | | 5 mM | 0.4780 mL | 2.3900 mL | 4.7800 mL | | 10 mM | 0.2390 mL | 1.1950 mL | 2.3900 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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture and light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 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 90%corn oil Solubility: ≥ 5 mg/mL (11.95 mM); Clear solution
此方案可获得 ≥ 5 mg/mL (11.95 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 50.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 2. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 4.25 mg/mL (10.16 mM); Suspended solution; Need ultrasonic
此方案可获得 4.25 mg/mL (10.16 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 42.5 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。 *以上所有助溶剂都可在本网站选购。
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