| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
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MLi-2 (MLi2) is a novel, highly potent, orally bioactive, and selective LRRK2 (Leucine-Rich Repeat Kinase 2) kinase inhibitor (IC50 = 0.76 nM) with CNS (central nervous system) activity, and thus has the potential for treating Parkinson's disease. 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.
| Targets |
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| ln Vitro |
MLi-2 demonstrates remarkable efficacy in three different assays: radioligand competition Binding (IC50=3.4 nM), cellular test monitoring LRRK2 pSer935 LRRK2 dephosphorylation (IC50=1.4 nM), and purified LRRK2 kinase assay in vitro (IC50=0.76 nM). Over 300 kinases, as well as a range of receptors and ion channels, are more than 295-fold selective for MLi-2 [1].
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| ln Vivo |
Dephosphorylation of pSer935 LRRK2 was used to measure the dose-dependent suppression of central and peripheral targets in MLi-2 mice treated acutely or subchronically over a 24-hour period. Over a period of 15 weeks, MLi-2 treatment in MitoPark mice resulted in well-tolerated brain and plasma exposure. MitoPark mice treated with MLi-2 showed alterations in lung morphology that were in line with increased type II pneumocytes [1].
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| References | ||
| Additional Infomation |
MLI-2 is a member of the class of indazoles that is 1H-indazole that is substituted at position 3 by a 6-(cis-2,6-dimethylmorpholin-4-yl)pyrimidin-4-yl group and at position 5 by a (1-methylcyclopropoxy)group. It is an inhibitor of leucine-rich repeat kinase 2 (LRRK2). It has a role as an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor. It is a member of indazoles, a member of pyrimidines, a member of morpholines, a member of cyclopropanes, an aromatic ether and a tertiary amino compound.
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| Molecular Formula |
C21H25N5O2
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|---|---|
| Molecular Weight |
379.4555
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| Exact Mass |
379.2
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| Elemental Analysis |
C, 66.47; H, 6.64; N, 18.46; O, 8.43
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| CAS # |
1627091-47-7
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| PubChem CID |
78319901
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
625.8±55.0 °C at 760 mmHg
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| Flash Point |
332.3±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.628
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| LogP |
3.42
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
549
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O(C1C([H])=C([H])C2=C(C(C3=C([H])C(=NC([H])=N3)N3C([H])([H])[C@@]([H])(C([H])([H])[H])O[C@@]([H])(C([H])([H])[H])C3([H])[H])=NN2[H])C=1[H])C1(C([H])([H])[H])C([H])([H])C1([H])[H]
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| InChi Key |
ATUUNJCZCOMUKD-OKILXGFUSA-N
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| InChi Code |
InChI=1S/C21H25N5O2/c1-13-10-26(11-14(2)27-13)19-9-18(22-12-23-19)20-16-8-15(28-21(3)6-7-21)4-5-17(16)24-25-20/h4-5,8-9,12-14H,6-7,10-11H2,1-3H3,(H,24,25)/t13-,14+
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| Chemical Name |
(2S,6R)-2,6-dimethyl-4-(6-(5-(1-methylcyclopropoxy)-1H-indazol-3-yl)pyrimidin-4-yl)morpholine
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| Synonyms |
MLi-2 MLi 2 MLi2.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~131.77 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.87 mg/mL (7.56 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.87 mg/mL (7.56 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 5: 5 mg/mL (13.18 mM) in 30 % SBE-β-CD (add these co-solvents sequentially from left to right, and one by one), Suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6353 mL | 13.1766 mL | 26.3532 mL | |
| 5 mM | 0.5271 mL | 2.6353 mL | 5.2706 mL | |
| 10 mM | 0.2635 mL | 1.3177 mL | 2.6353 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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