URMC-099
分子式：C₂₇H₂₇N₅分子量：421.54
简介 ：URMC-099 是一种口服生物有效的混合谱系激酶 3 (MLK3) (IC50=14 nM) 抑制剂，具有优异的血脑屏障穿透性。
物理性状及指标：
外观：……………………粉末
溶解性：…………………DMSO : ≥ 33 mg/mL (78.28 mM)；H2O : < 0.1 mg/mL (insoluble)
含量：……………………>98%,BR
储存条件：-20°C，避光防潮密闭干燥
运输条件：2~8℃运输
生物活性
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描述
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URMC-099 is an orally bioavailable and potent mixed lineage kinase type 3 (MLK3) (IC50=14 nM) inhibitor with with excellent blood-brain barrier penetration properties.
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IC50 & Target
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I
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MLK3
14 nM (IC50)
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LRRK2
11 nM (IC50)
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FLT3
4 nM (IC50)
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FLT1
39 nM (IC50)
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ABL1 (T315I)
3 nM (IC50)
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ABL1
6.8 nM (IC50)
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SGK
67 nM (IC50)
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SGK1
201 nM (IC50)
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AurA
108 nM (IC50)
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AurB
123 nM (IC50)
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AurC
290 nM (IC50)
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IKKβ
257 nM (IC50)
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IKKα
591 nM (IC50)
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TNFα
460 nM (IC50)
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ROCK1
1030 nM (IC50)
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ROCK2
111 nM (IC50)
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CDK1
1125 nM (IC50)
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CDK2
1180 nM (IC50)
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TRKA
85 nM (IC50)
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c-MET
177 nM (IC50)
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TRKB
217 nM (IC50)
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IGF1R
307 nM (IC50)
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LCK
333 nM (IC50)
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MEKK2
661 nM (IC50)
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SYK
731 nM (IC50)
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AMPK
1512 nM (IC50)
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JNK1
3280 nM (IC50)
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SRC
4330 nM (IC50)
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ZAP70
5050 nM (IC50)
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ERK2
6290 nM (IC50)
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P38α
12050 nM (IC50)
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CYP3A4
16.2 μM (IC50)
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体外
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The effect of URMC-099 (URMC099) on the in vitro growth of the “brain homing” MDA-MB-231 BR cells expressing eGFP (eGFP8.4) and their parental cell line, MDA-MB-231 is tested. The cells are treated with either 200 nM URMC-099 or vehicle alone. Cells treated with URMC-099 grow at a similar rate to those treated with vehicle. Cell viability is >99% in all cases.
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体内
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URMC-099 has moderate terminal elimination half-life (t1/2=1.92 h, 2.14 h and 2.72 h for C57 BL/6 mice (10 mg/kg, oral dosing), C57 BL/6 mice (2.5 mg/kg, iv), C57 BL/6 mice (10 mg/kg, iv)). The effect of URMC-099 (URMC099) on tumor formation in vivo is analyzed using a well characterized mouse xenograft model of breast cancer brain metastasis. For these experiments, eGFP8.4 cells are inoculated into the left ventricle of immunodeficient nu/nu mice; animals are then treated with either URMC-099 (10 mg/kg) or vehicle alone, every 12 hours for 20 days. This dose of URMC-099 is chosen because it has been shown to be sufficient to effectively inhibit MLK3 in mice, with good penetration of the blood-brain barrier and potent inhibition of the phosphorylation of Jun N-terminal kinase (JNK) in brain tissue. On day 21 the mice are sacrificed and number of BM is assessed. Fifteen mice are used for each treatment group. BM are detected in 60% of mice, which is consistent with previous studies using this xenograft model by other investigators. URMC-099 treatment significantly (p<0.05, two-tailed t-test) increases the total number of brain metastasis (BM) in mice. For micrometastases, the pattern is similar to that observed for total BM. The number of macrometastases is statistically indistinguishable between mice treated with URMC-099 or vehicle.
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实验参考方法（仅来自公开文献，供参考）
| 细胞实验： |
MDA-MB-231, MCF10A, HS578t and MDA-MB-231 EGFP8.4 cells are seeded in a 24 well plate at an initial density of 5.0×104 cells/mL in 0.5 mL of media. The cells are treated with either 200 µM of URMC-099 or vehicle (0.002% DMSO). Cell number in each well is measured by trypsinizing the cells and counting them with a hematocytometer. The viability is tested by trypan blue dye exclusion. Each condition is tested in triplicate.
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动物实验
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Mice
6 to 8 week old female nu/nu mice are injected intraperitoneally with URMC-099 at a dose of 10 mg/kg, or vehicle, twice daily for 20 days. On day 21 mice are sacrificed by CO2 suffocation. Brains are removed and fixed with 4% formaldehyde in PBS overnight, then transferred to 30% sucrose in PBS. The brains are then quickly frozen by immersing into isopentane cooled on dry ice. The frozen brains are sectioned coronally every 30 micrometers. Eight sections starting at bregma 2.0 and separated by 360 µm are mounted on glass slides for tumor evaluation under the microscope. The number of brain metastasis (BM) is counted by examining eGFP signals under a fluorescence microscope at 20× magnification.
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储液配置及储存： 按表中溶解性配置；如溶解困难，可以通过快速搅拌，超声或温和加热（在45-60°C下水浴）。液体稳定性报道的很少，建议现配现用，如需储存，建议：-20℃1-3月；-80℃ 3-6月。
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1 mg
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5 mg
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10 mg
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1 mM
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2.3723 mL
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11.8613 mL
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23.7225 mL
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5 mM
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0.4745 mL
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2.3723 mL
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4.7445 mL
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10 mM
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0.2372 mL
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1.1861 mL
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2.3723 mL
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【注意 】
●我司产品为非无菌包装，若用于细胞培养，请提前做预处理，除去热原细菌，否则会导致染菌。
●部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，以上数据仅供参考交流研究之用。
我司所售出产品仅供于科研研究用途（非临床科研研究），每次销售产品行为都适用于我司网上所列明的。
CAS 号：1229582-33-5
英文名字：URMC-099
质量标准：>98%,BR
分子式：C27H27N5
