TD52 是 Erlotinib (HY-50896) 衍生物，一种具有口服活性的强效癌性蛋白磷酸酶 2A (CIP2A) 抑制剂。TD52 通过调节 CIP2A/PP2A/p-Akt 信号通路介导三阴性乳腺癌 (TNBC) 细胞的凋亡作用。TD52 通过干扰 Elk1 与 CIP2A 启动子的结合间接减少 CIP2A。TD52 具有小的 p-EGFR 抑制作用并具有抗癌活性。
| 生物活性 | TD52, an Erlotinib (HY-50896) derivative, is an orally active, potent cancerous inhibitor ofproteinphosphatase2A (CIP2A)inhibitor. TD52 mediates theapoptoticeffect in triple-negative breastcancer(TNBC) cells via regulating the CIP2A/PP2A/p-Akt signalling pathway. TD52 indirectly reduced CIP2A by disturbing Elk1 binding to the CIP2A promoter. TD52 has less p-EGFR inhibition and has potent anti-cancer activity[1]. |
体外研究
(In Vitro) | TD52 (2-10 μM; 48 hours) shows anti-proliferative ability and induces differential apoptotic effects in these cell lines[1].
TD52 (5 μM; 48 hours) has minimal effects on p-EGFR or EGFR expression but downregulated CIP2A expression[1].
TD52 (2.5, 5, 7.5 μM; 48 hours) time-dependently induces apoptosis accompanied with downregulating CIP2A and p-Akt[1].
TD52 (5 μM; 24 hours) significantly increases the phosphatase activity of PP2A in TNBC cells[1].
TD52 (5 μM; 48 hours) has no obvious effects on other common RTKs, such as IGFR, PDGFR and VEGFR2[1].
Apoptosis Analysis[1] | Cell Line: | Three TNBC cell lines including HCC-1937, MDA-MB-231 and MDA-MB-468 cells | | Concentration: | 2, 4, 6, 8, 10 μM | | Incubation Time: | 48 hours | | Result: | Showed anti-proliferative ability and induced differential apoptotic effects in these cell lines. |
Western Blot Analysis[1] | Cell Line: | MDA-MB-231 cell | | Concentration: | 5 μM | | Incubation Time: | 48 hours | | Result: | Had minimal effects on p-EGFR or EGFR expression but downregulated CIP2A expression. |
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体内研究
(In Vivo) | TD52 (10 mg/kg/day; oral gavage; for 52 days) significantly inhibits MDA-MB-468 xenograft tumour size and tumour weight[1].
| Animal Model: | Female NCr athymic nude mice (5-7 weeks of age)[1] | | Dosage: | 10 mg/kg | | Administration: | Oral gavage; daily; for 52 days | | Result: | Significantly inhibits MDA-MB-468 xenograft tumour size and tumour weight.
Decreased the protein expressions of CIP2A and p-Akt in the three MDA-MB-468 xenograft tumours. |
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| 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 |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(277.46 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.7746 mL | 13.8731 mL | 27.7462 mL | | 5 mM | 0.5549 mL | 2.7746 mL | 5.5492 mL | | 10 mM | 0.2775 mL | 1.3873 mL | 2.7746 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。-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 40%PEG300 5%Tween-80 45% saline Solubility: 2.5 mg/mL (6.94 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (6.94 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 25.0 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (6.94 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (6.94 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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