Tolimidone-MLR-1023-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETolimidoneCat. No.: HY-59047CAS No.: 41964-07-2Synonyms: MLR-1023分式: CHNO分量: 202.21作靶点: Src作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 150 mg/mL (741.80

2、mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 4.9454 mL 24.7268 mL 49.4535 mL5 mM 0.9891 mL 4.9454 mL 9.8907 mL10 mM 0.4945 mL 2.4727 mL 4.9454 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，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备

3、液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (12.36 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (12.36 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Mo

4、lecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (12.36 mM); Clear solution; Need warmingBIOLOGICAL ACTIVITY物活性 Tolimidone个有效且有选择性的 Lyn kinase 变构激活剂，其 EC50 值为 63 nM。IC50 & Target EC50: 63 nM (Lyn kinase) 1体外研究 Incubation of Tolimidone (MLR-1023) with Lyn kinase elicits a repeatable 50% increase in e

5、nzyme activity.Tolimidone elicits a concentration-dependent increase in Lyn kinase activation with a 2.3- and 2.1-foldincrease achieved at concentrations of 3 and 10 M, respectively. Inclusion of Tolimidone (100 M)increases Lyn kinase activity by 3-fold at each ATP concentration tested (Vmax=2601 U/

6、mg). Tolimidone-mediated activation of Lyn kinase increases in proportion to the length of preincubation period in the absenceof ATP 1.体内研究 Administration of Tolimidone (MLR-1023) (30 mg/kg i.p.) significantly (p 1. Tolimidone elicits a dose-dependent potentiation of the insulin response, with a max

7、imal effect observed with a dose level of 30 mg/kg2.PROTOCOLKinase Assay 1 For each kinase assay, Tolimidone (MLR-1023) (10 M) is preincubated with kinase and fluoroscein-labeledprotein substrate. The reaction is initiated with the addition of ATP (at a concentration at or below the Km foreach kinas

8、e), and the level of fluoroscein phosphopeptide is measured. The assays are conducted induplicate 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Adipocyte differentiation is assessed in mouse 3T3-L1 cells after 8 days of incubation with

9、Tolimidone (MLR-1023) or rosiglitazone (10 M). PPAR (, and ) transactivation studies are conducted in transientlytransfected cells containing the appropriate DNA constructs (pGAL4/PPAR, or ) cotransfected with aluciferase reporter vector. Tolimidone or an appropriate reference compound is incubated

10、with transfectedcells for 24 h. Luciferase activity is monitored as a measure of PPAR, and activation 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male mice, 8 to 10 weeks of age, are used in studies of baseline glucose, glucose tolerance, a

11、nd insulinAdministration 1 levels. Tolimidone (MLR-1023) is administered intraperitoneally at dose volumes of 5 to 10 mL/kg. Blood (5 L) is acquired from a tail snip and directly applied to a glucose test strip. Blood levels of Tolimidone aremeasured by liquid chromatography/tandem mass spectrometry

12、, and levels are determined by comparingthem with a standard curve of Tolimidone prepared in blood 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE1. Saporito MS, et al. MLR-1023 is a potent a

13、nd 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 durableimprovement in glucose homeostasis in animal models of type 2 diabetes. J Pharmacol Exp Ther. 2012 Jul;342(1):23-32.Mc