| CAS |
No.41964-07-2 |
| 中文名称 |
托利咪酮 |
| 英文名称 |
MLR-1023 |
| 别名 |
CP-26154;NSC 314335;Tolimidone |
| 分子式 |
C11H10N2O2 |
| 分子量 |
202.21 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD00866900 |
| SMILES |
CC1=CC(=CC=C1)OC2=CNC(=O)N=C2 |
| InChIKey |
HJQILFPVRNHTIG-UHFFFAOYSA-N |
| InChI |
InChI=1S/C11H10N2O2/c1-8-3-2-4-9(5-8)15-10-6-12-11(14)13-7-10/h2-7H，1H3，(H，12，13，14) |
| PubChem CID |
39065 |
| 靶点 |
Lyn kinase |
| 通路 |
Protein Tyrosine Kinase/RTK |
| 背景说明 |
Tolimidone 是一个有效且有选择性的 Lyn kinase 变构激活剂。 |
| 生物活性 |
Tolimidone is a potent and selective allosteric activator of Lyn kinase with an EC50 of 63 nM.[1-2] |
| IC50 |
EC50: 63 nM (Lyn kinase)[1] |
| In Vitro |
Incubation of Tolimidone (MLR-1023) with Lyn kinase elicits a repeatable 50% increase in enzyme activity. Tolimidone elicits a concentration-dependent increase in Lyn kinase activation with a 2.3- and 2.1-fold increase achieved at concentrations of 3 and 10 μM， respectively. Inclusion of Tolimidone (100 μM) increases Lyn kinase activity by 3-fold at each ATP concentration tested (Vmax=2601 U/mg). Tolimidone-mediated activation of Lyn kinase increases in proportion to the length of preincubation period in the absence of ATP[1]. |
| In Vivo |
Administration of Tolimidone (MLR-1023) (30 mg/kg i.p.) significantly (padiponectin production by 3.7- and 19-fold， respectively[1]. Tolimidone elicits a dose-dependent potentiation of the insulin response， with a maximal effect observed with a dose level of 30 mg/kg[2]. |
| 细胞实验 |
Adipocyte differentiation is assessed in mouse 3T3-L1 cells after 8 days of incubation with Tolimidone (MLR-1023) or rosiglitazone (10 μM). PPAR (α， σ and γ) transactivation studies are conducted in transiently transfected cells containing the appropriate DNA constructs (pGAL4/PPARα， σ or γ) cotransfected with a luciferase reporter vector. Tolimidone or an appropriate reference compound is incubated with transfected cells for 24 h. Luciferase activity is monitored as a measure of PPARα， σ and γ activation[1]. |
| 动物实验 |
Male mice， 8 to 10 weeks of age， are used in studies of baseline glucose， glucose tolerance， and insulin levels. Tolimidone (MLR-1023) is administered intraperitoneally at dose volumes of 5 to 10 mL/kg. Blood (5 μL) is acquired from a tail snip and directly applied to a glucose test strip. Blood levels of Tolimidone are measured by liquid chromatography/tandem mass spectrometry， and levels are determined by comparing them with a standard curve of Tolimidone prepared in blood[1]. |
| 激酶实验 |
For each kinase assay， Tolimidone (MLR-1023) (10 μM) is preincubated with kinase and fluoroscein-labeled protein substrate. The reaction is initiated with the addition of ATP (at a concentration at or below the Km for each kinase)， and the level of fluoroscein phosphopeptide is measured. The assays are conducted in duplicate[1]. |
| 数据来源文献 |
[1]. Saporito MS， et al. MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo. J Pharmacol Exp Ther. 2012 Jul;342(1):15-22.
[2]. Ochman AR， et al. The Lyn kinase activator MLR-1023 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes. J Pharmacol Exp Ther. 2012 Jul;342(1):23-32. |
| 规格 |
5mg 10mg 25mg 50mg 100mg |
| 单位 |
瓶 |
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英语
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