MLi-2

製品コードS9694 バッチS969402

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C21H25N5O2
分子量 379.46 CAS No. 1627091-47-7
Solubility (25°C)* 体外 DMSO 76 mg/mL (200.28 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5% DMSO 95% Corn oil
1.9mg/ml Taking the 1 mL working solution as an example, add 50 μL of 38 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
1.9mg/ml Taking the 1 mL working solution as an example, add 50 μL of 38 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 MLi-2 is an orally active and highly selective inhibitor of LRRK2. MLi-2 exhibits exceptional potency in a purified LRRK2 kinase assay in vitro with IC50 of 0.76 nM, a cellular assay monitoring dephosphorylation of LRRK2 pSer935 LRRK2 with IC50 of 1.4 nM, and a radioligand competition binding assay with IC50 of 3.4 nM.
in vitro

MLi-2 is a structurally novel, highly potent, and selective LRRK2 kinase inhibitor with central nervous system activity. MLi-2 exhibits exceptional potency in a purified LRRK2 kinase assay in vitro (IC50 = 0.76 nM), a cellular assay monitoring dephosphorylation of LRRK2 pSer935 LRRK2 (IC50 = 1.4 nM), and a radioligand competition binding assay (IC50 = 3.4 nM). MLi-2 has greater than 295-fold selectivity for over 300 kinases in addition to a diverse panel of receptors and ion channels.[1]
in vivo

Acute oral and subchronic dosing in MLi-2 mice resulted in dosedependent central and peripheral target inhibition over a 24-hour period as measured by dephosphorylation of pSer935 LRRK2. Treatment of MitoPark mice with MLi-2 is well tolerated over a 15-week period at brain and plasma exposures >100× the in vivo plasma IC50 for LRRK2 kinase inhibition as measured by pSer935 dephosphorylation. Morphologic changes in the lung, consistent with enlarged type II pneumocytes, are observed in MLi-2-treated MitoPark mice.[1]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 SH-SY5Y cells
濃度 10 serial 3-fold dilutions, top concentration 5 μM
反応時間 90 min
実験の流れ

A human neuroblastoma cell line, SH-SY5Y, is used for the LRRK2 stable cell line construction. SH-SY5Y cells are cultured in Dulbecco’s modified Eagle’s medium/F-12 supplemented with GlutaMax, 10% tetracycline (Tet)-free fetal bovine serum, nonessential amino acids, pen-strep at 37°C and 5% carbon dioxide. Parental cells are transfected with plasmid constructs that overexpress full-length human LRRK2 wildtype or mutant (G2019S) under the control of a Tet-inducible promoter. Transfected cells are selected and maintained with hygromycin (2 mg/ml) and zeocin (100 mg/ml). Cells are seeded into six-well plates and induced with Tet (2 mg/ml) for 72 hours prior to treatment. After 90 minutes of MLi-2 incubation, cells were mechanically lifted, pelleted, and lysed with lysis buffer supplemented with protease, and phosphatase inhibitors. Pellets are further bead homogenized and then spun at 13,200 rpm for 20 minutes at 4°C. Supernatants are then removed for subsequent Western blot analyses.
動物実験 動物モデル male C57Bl/6 mice
投薬量 1 mg/kg, 2 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg
投与方法 IV, Oral gavage

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Pharmacological Inhibition of LRRK2 Exhibits Neuroprotective Activity in Mouse Photothrombotic Stroke Model [ Exp Neurobiol, 2024, 33(1):36-45] PubMed: 38471803

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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