RG7112 是有效的、选择性的、第一个用于临床的、可口服的、可透过血脑屏障的、MDM2-p53抑制剂，IC50值为 18 nM，结合到MDM2 的KD值为 11 nM.
| 生物活性 | RG7112 is a potent, selective, first clinical, orally active and blood-brain barrier crossedMDM2-p53inhibitor, with anIC50of 18 nM and aKDof 11 nM for binding toMDM2[1]. |
| IC50& Target | |
体外研究
(In Vitro) | RG7112 (0-5 μM) stabilizes wild-type p53 and induces p53 signaling in cancer cells. RG7112 effectively activates p53 functions in cancer cells[1][2].
Cell Proliferation Assay[2] | Cell Line: | SJSA1 osteosarcoma cells. | | Concentration: | 0-5 μM. | | Incubation Time: | 0-60 hours. | | Result: | Dose-dependently inhibited the growth and killed SJSA1 osteosarcoma cells expressing high levels of MDM2 protein due to MDM2 gene amplification. |
Cell Cycle Analysis[2] | Cell Line: | HCT116 and SJSA1 cells. | | Concentration: | 0-5 μM. | | Incubation Time: | 48 hours. | | Result: | Induced a dose-dependent cell cycle block in G1 and G2/M phase and depletion of the S phase compartment. |
|
体内研究
(In Vivo) | RG7112 (25-200 mg/kg, single oral dose) activates p53 pathway and induces apoptosis in tumor cells in vivo[2].
RG7112 (100 mg/kg, gavage once per day, 5 days/week for 3 weeks ) reduces tumor growth rate and increases survival in GBM models[3].
| Animal Model: | Female Balb/c nude mice[2]. | | Dosage: | 25-200 mg/kg. | | Administration: | Orally, single dose. | | Result: | At the highest dose level of RG7112 (200 mg/kg) only 1.2% (± 0.89 SD) of cells incorporated BrdU at 24 h post-dosing, vs. 14% (± 1.83 SD) of vehicle treated tumors. |
| Animal Model: | GBM cells were implanted into the brain of Athymic Nude mice (7 weeks old females, 10 animals/group)[3]. | | Dosage: | 100 mg/kg. | | Administration: | Oral gavage, once per day, 5 days/week for 3 weeks. | | Result: | Reduced tumor growth rate and increases survival in heterotopic and orthotopic animal models bearing MDM2-amplified GBM. |
|
| Clinical Trial | |
| 分子量 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 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 : 200 mg/mL(274.81 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.3740 mL | 6.8702 mL | 13.7404 mL | | 5 mM | 0.2748 mL | 1.3740 mL | 2.7481 mL | | 10 mM | 0.1374 mL | 0.6870 mL | 1.3740 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: ≥ 10 mg/mL (13.74 mM); Clear solution
此方案可获得 ≥ 10 mg/mL (13.74 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 100.0 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%corn oil Solubility: ≥ 10 mg/mL (13.74 mM); Clear solution
此方案可获得 ≥ 10 mg/mL (13.74 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 100.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 3. 请依序添加每种溶剂： 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: ≥ 5 mg/mL (6.87 mM); Clear solution 4. 请依序添加每种溶剂： 5% DMSO 95% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (3.44 mM); Clear solution *以上所有助溶剂都可在本网站选购。
|
m.cnreagent.com