MRT199665 是一种有效的，ATP竞争性的，选择性MARK/SIK/AMPK抑制剂，对MARK1/MARK2/MARK3/MARK14，AMPKα1/AMPKα2和SIK1/SIK2/SIK3的IC50分别为 2/2/3/2 nM，10/10 nM 和 110/12/43 nM。MRT199665 作用于 MEF2C 激活的人急性髓性白血病 (AML) 细胞，引起凋亡 (apoptosis)。MRT199665 抑制 SIK 底物 CRTC3 磷酸化 (在 S370 位点)。
| 生物活性 | MRT199665 is a potent and ATP-competitive, selectiveMARK/SIK/AMPKinhibitor withIC50s of 2/2/3/2 nM, 10/10 nM, and 110/12/43 nM forMARK1/MARK2/MARK3/MARK14,AMPKα1/AMPKα2, andSIK1/SIK2/SIK3, respectively[1]. MRT199665 causesapoptosisin MEF2C-activated human acute myeloid leukemias (AML) cells[2]. MRT199665 inhibits the phosphorylation of SIK substrate CRTC3 at S370[3]. |
| IC50& Target | MARK1 2 nM (IC50) | MARK2 2 nM (IC50) | MARK3 3 nM (IC50) | MARK4 2 nM (IC50) | SIK1 110 nM (IC50) | SIK2 12 nM (IC50) | SIK3 43 nM (IC50) | NUAK1 3 nM (IC50) | NUAK2 120 nM (IC50) | AMPKα1 10 nM (IC50) | AMPKα2 10 nM (IC50) | MELK 29 nM (IC50) | TBK1 5400 nM (IC50) | IKKε 7700 nM (IC50) | BRSK2 10000 nM (IC50) |
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体外研究
(In Vitro) | MRT199665 (1 μM; pre-treated for 1 h) increases LPS (100 ng/mL; stimulated for up to 24 h)-stimulated IL-10 mRNA and Nurr77 mRNA production, and IL-10 secretion[1].
MRT199665 (1 nM-100 μM; 48 hours) reduces leukemia growth[2].
MRT199665 treatment can block MEF2C S222 phosphorylation in acute myeloid leukemias (AML) cells.
MRT199665 (10 nM-1000 nM; 12 hours) leads to a dose-dependent reduction in total and pS222 MEF2C. MRT199665 also causes a decrease of total MEF2C protein[2].
Western Blot Analysis[2] | Cell Line: | OCI-AML2 and MOLM-13 cells | | Concentration: | 10, 100, 500, and 1000 nM | | Incubation Time: | 12 hours | | Result: | Led to a dose-dependent reduction in total and pS222 MEF2C, causing more than 40% reduction in MEF2C phosphorylation at 10 nM as compared to untreated cells. |
Cell Proliferation Assay[2] | Cell Line: | Human AML cell lines OCI-AML2, MV4-11, MOLM-13 and Kasumi-1 with endogenous MEF2C phosphorylation; human AML cell lines NB-4, HEL, HL-60 and U937 lacking MEF2C | | Concentration: | 1 nM, 10 nM, 100n M, 1 μM, 10 μM, 100μM | | Incubation Time: | 48 hours | | Result: | Human AML cell lines with endogenous MEF2C phosphorylation (OCI-AML2, MV4–11, MOLM-13 and Kasumi-1) were more sensitive as compared to cell lines lacking MEF2C (NB-4, HEL, HL-60 and U937), with mean IC50of 26±13 versus 990±29 nM, 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 : 125 mg/mL(266.20 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.1296 mL | 10.6478 mL | 21.2956 mL | | 5 mM | 0.4259 mL | 2.1296 mL | 4.2591 mL | | 10 mM | 0.2130 mL | 1.0648 mL | 2.1296 mL |
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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
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此方案可获得 ≥ 2.08 mg/mL (4.43 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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: ≥ 2.08 mg/mL (4.43 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.43 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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: ≥ 2.08 mg/mL (4.43 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.43 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 20.8 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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