SIAIS178 是一种PROTAC类的有效的，选择性的BCR-ABL降解剂，IC50为 24 nM。SIAIS178 通过募集Von Hippel-Lindau(VHL) E3 泛素连接酶来降解 BCR-ABL 蛋白。SIAIS178 具有抗肿瘤活性。
| 生物活性 | SIAIS178 is a potent and selectiveBCR-ABLdegrader based onPROTACtechnology with anIC50of 24 nM. SIAIS178 causes effective degradation ofBCR-ABLprotein by recruitingVon Hippel-Lindau(VHL) E3 ubiquitin ligase. SIAIS178 has anticancer activity[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | SIAIS178 (1-100 nM; for 16 hours) significantly reduces the BCR-ABL protein levels in a concentration dependent manner. SIAIS178 significantly inhibits the phosphorylation of BCR-ABL and the substrates STAT5[1].
SIAIS178 (1, 10, 100, 1000 nM) exerts significant antiproliferative activity in BCR-ABL driven CML cell lines. SIAIS178 retains potency and selectivity against the BCR-ABL driven cell lines[1].
Western Blot Analysis[1] | Cell Line: | K562 cells | | Concentration: | 1, 3, 10, 30, 100 nM | | Incubation Time: | 16 hours | | Result: | Significantly reduced the BCR-ABL protein levels in a concentration dependent manner. |
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体内研究
(In Vivo) | SIAIS178 (ip; 5, 15, and 45 mg/kg; 12 days) attenuates tumor progression in a dose-dependent manner, as determined by serial volumetric measurement[1].
SIAIS178 (iv or ip; 2 mg/kg; 24 hours) has T1/2of 3.82 and 12.35 hours and Cmaxof 1165.2 nM and 30 nM for iv and ip, respectively[1].
| Animal Model: | NOD/SCID mice with termed K562-Luc[1] | | Dosage: | 5, 15, and 45 mg/kg | | Administration: | Ip; 12 days | | Result: | Attenuated tumor progression in a dose-dependent manner, as determined by serial volumetric measurement. |
| Animal Model: | Female Wistar rats[1] | | Dosage: | 2 mg/kg (Pharmacokinetic Analysis) | | Administration: | Iv or ip; 24 hours | | Result: | Had T1/2of 3.82 and 12.35 hours and Cmaxof 1165.2 nM and 30 nM for iv and ip, respectively. |
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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 : 300 mg/mL(296.24 mM;Need ultrasonic) 配制储备液 | 1 mM | 0.9875 mL | 4.9374 mL | 9.8748 mL | | 5 mM | 0.1975 mL | 0.9875 mL | 1.9750 mL | | 10 mM | 0.0987 mL | 0.4937 mL | 0.9875 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: ≥ 7.5 mg/mL (7.41 mM); Clear solution
此方案可获得 ≥ 7.5 mg/mL (7.41 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 75.0 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。 *以上所有助溶剂都可在本网站选购。
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