RKI 1447 dihydrochloride 是一种有效的选择性ROCK抑制剂，对ROCK1和ROCK2的IC50分别为 14.5 和 6.2 nM。RKI 1447 dihydrochloride 抑制结直肠癌细胞的生长并促进细胞凋亡 (apoptosis)。
| 生物活性 | RKI 1447 dihydrochloride is a potent and selectiveROCKinhibitor withIC50s of 14.5 and 6.2 nM forROCK1andROCK2, respectively[1]. RKI 1447 dihydrochloride suppresses colorectal carcinoma cell growth and promotesapoptosis[2]. |
| IC50& Target[1][2] | ROCK1 14.5 nM (IC50) | ROCK2 6.2 nM (IC50) | Apoptosis |
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体外研究
(In Vitro) | RKI 1447 suppresses phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells, but has no effect on the phosphorylation levels of the AKT, MEK, and S6 kinase at concentrations as high as 10 μM[1].
RKI 1447 (0.003-10 μM) is potent at inhibiting the phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells[1].
RKI 1447 exhibits effective anticancer activity in colorectal carcinoma (CRC). RKI 1447 (10-320 μM; 24 hours) drastically suppresses HCT-8 and HCT-116 cell growth[2].
RKI 1447 (20-80 μM; 24 hours) induces apoptosis in a dose-dependent manner[2].
Cell Viability Assay[2] | Cell Line: | CRC cell lines HCT-8 and HCT-116 cells | | Concentration: | 0, 10, 20, 40, 80, 160, 320 μM | | Incubation Time: | 24 hours | | Result: | HCT-8 and HCT-116 viability was drastically decreased in a dose-dependent manner. |
Apoptosis Analysis[2] | Cell Line: | CRC cell lines HCT-8 and HCT-116 cells | | Concentration: | 0, 20, 40, 80 μM | | Incubation Time: | 24 hours | | Result: | Treatment promoted apoptosis. |
Western Blot Analysis[1] | Cell Line: | MDA-MB-231 human breast cancer cells | | Concentration: | 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3 ,10 μM | | Incubation Time: | | | Result: | Decreased the levels of P-MLC-2, but not total MLC-2, in a concentration-dependent manner with significant effects starting at 100 nM. |
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体内研究
(In Vivo) | RKI 1447 (200 mg/kg; i.p. daily for 14 days) inhibits mammary tumor growth in vivo[1].
RKI 1447 (100 mg/kg; i.p.; once every 3 days; for 14 days) exerts antitumor activity on CRC in vivo. RKI 1447 does not exert physiological toxicity on the mice[2].
| Animal Model: | MMTV/neu transgenic mice [FVB/N-Tg (MMTVneu) 202 Mul/J][1] | | Dosage: | 200 mg/kg | | Administration: | Treated i.p. daily for 14 days | | Result: | Tumors from mice treated with vehicle increased in size with an average percent change in tumor volume of 68.3%. In contrast, tumors from mice treated with the RKI-1447 increased in size with an average percent change in tumor volume of only 8.8%. Thus, RKI-1447 inhibited mammary tumor growth by 87%. |
| Animal Model: | 5-week-old Male BALB/C nude mice[2] | | Dosage: | 100 mg/kg | | Administration: | Intraperitoneally injected; once every 3 days; for 14 days | | Result: | Efficiently blocked CRC tumor growth in vivo. |
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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 : 50 mg/mL(125.22 mM;Need ultrasonic) H2O :< 0.1 mg/mL (ultrasonic;warming;heat to 60℃)(insoluble) 配制储备液 | 1 mM | 2.5044 mL | 12.5222 mL | 25.0445 mL | | 5 mM | 0.5009 mL | 2.5044 mL | 5.0089 mL | | 10 mM | 0.2504 mL | 1.2522 mL | 2.5044 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 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (6.26 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.26 mM，饱和度未知) 的澄清溶液。 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 (6.26 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.26 mM，饱和度未知) 的澄清溶液。 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。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (6.26 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.26 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 25.0 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本网站选购。
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