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MLi-2

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Chemical Structure| 1627091-47-7 同义名 : -
CAS号 : 1627091-47-7
货号 : A303998
分子式 : C21H25N5O2
纯度 : 99%+
分子量 : 379.455
MDL号 : MFCD30536362
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(131.77 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The leucine-rich repeat kinase 2 (LRRK2) is commonly mutated in familial and sporadic Parkinson’s disease. Merck LRRK2 inhibitor-2 (MLi-2) is a potent and selective LRRK2 inhibitor with an IC50 value of 0.76nM in a purified LRRK2 kinase assay in vitro. It also exhibited high potency in a cellular assay monitoring the dephosphorylation of pSer935 LRRK2 and a radioligand competition binding assay with IC50 values of 1.4nM and 3.4nM, respectively. In mice, oral administration of MLi-2 dose-dependently reduced phosphorylation of Ser935 with the maximal suppression (>90% reduction) observed at 10mg/kg and higher. The in-diet administration of MLi-2 (3–120mg/kg/day) for 11 days significantly reduced LRRK2 protein level in the kidneys of mice. Treatment with MLi-2 (30mg/kg/day) markedly inhibited pSer935 LRRK2 in the brains of MitoPark mice at 3, 9, and 15 weeks of treatment compared with the vehicle-treated group, but did not stop the progressive motor phenotype or prevented the decline in striatal dopamine, DOPAC, or tyrosine hydroxylase levels in MitoPark mice[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.64mL

0.53mL

0.26mL

13.18mL

2.64mL

1.32mL

26.35mL

5.27mL

2.64mL
参考文献

[1]Scott JD, DeMong DE, et al. Discovery of a 3-(4-Pyrimidinyl) Indazole (MLi-2), an Orally Available and Selective Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitor that Reduces Brain Kinase Activity. J Med Chem. 2017 Apr 13;60(7):2983-2992.

[2]Cikes M. Variations in expression of surface antigens on cultured cells. Ann N Y Acad Sci. 1971 Jun 21;177:190-200.

[3]Fell MJ, Mirescu C, Basu K, Cheewatrakoolpong B, DeMong DE, Ellis JM, Hyde LA, Lin Y, Markgraf CG, Mei H, Miller M, Poulet FM, Scott JD, Smith MD, Yin Z, Zhou X, Parker EM, Kennedy ME, Morrow JA. MLi-2, a Potent, Selective, and Centrally Active Compound for Exploring the Therapeutic Potential and Safety of LRRK2 Kinase Inhibition. J Pharmacol Exp Ther. 2015 Dec;355(3):397-409.