| 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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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
GNE-7915 tosylate targets leucine-rich repeat kinase 2 (LRRK2), an enzyme implicated in Parkinson's disease pathogenesis. Mutations in LRRK2 are one of the most common genetic causes of familial Parkinson's disease. By inhibiting LRRK2 kinase activity, GNE-7915 reduces the phosphorylation of LRRK2 substrates, potentially slowing or preventing neurodegeneration. The compound has an IC50 of 9 nM for LRRK2.
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| ln Vitro |
For GNE-7915 and compound 19, single-digit nanomolar LRRK2 cellular activity are obtained by keeping the methoxy/fluoro arrangement at C-2′/C-5′ and altering the aminoalkyl R1 substitution. Only TTK exhibits more than 50% inhibition in expanded Invitrogen kinase profiling (187 kinases) at 0.1 μM for GNE-7915 (100-fold over LRRK2 Ki) and 19 (250-fold over LRRK2 Ki). For GNE-7915 at 0.1 μM, selectivity profiling is also carried out utilizing the DiscoverX KinomeScan55 competitive binding test panel, which contains 392 distinct kinases. Further corroborating the good LRRK2 selectivity for GNE-7915 is the detection of binding of >65% for just LRRK2, TTK, and ALK, and of >50% for ten other kinases. Expanded brain panels and cerep receptor profiling indicate that GNE-7915 and 19 only inhibit 5-HT2B with >70% inhibition at 10 μM. In vitro functional studies have demonstrated that GNE-7915 and 19 are moderately effective 5-HT2B antagonists[2].
In vitro, GNE-7915 tosylate is a potent and selective LRRK2 inhibitor with an IC50 of 9 nM. The compound is brain-penetrant, making it suitable for studying central nervous system targets. Specific cellular assay data, such as IC50 values for inhibition of LRRK2-mediated phosphorylation in cells, are not detailed in the available sources. The compound's selectivity over other kinases has been characterized in kinase panel screening. |
| ln Vivo |
In rats, GNE-7915 demonstrates excellent in vivo PK profiles with long half-lives, good oral exposure and high passive permeability. GNE-7915 (50 mg/kg i.p. or p.o.) results in concentration-dependent knockdown of pLRRK2 in the brain of BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation.
GNE-7915 tosylate is a brain-penetrant LRRK2 inhibitor used in research related to Parkinson's disease. As a potent and selective LRRK2 inhibitor with brain penetration, it is expected to have in vivo activity in animal models of Parkinson's disease. Specific animal model data are not detailed in the available sources. The compound is intended for research use only. |
| Enzyme Assay |
The LRRK2 kinase inhibition assay for GNE-7915 involves incubating the compound with recombinant LRRK2 kinase, ATP, and a peptide substrate (such as a LRRKtide substrate). The reaction is carried out in a kinase buffer optimized for LRRK2 activity. After incubation, the amount of phosphorylated substrate is quantified using a luminescence-based kinase assay (such as ADP-Glo) or a radiometric assay. IC50 values are calculated from dose-response curves. Selectivity is assessed by testing against a panel of kinases.
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| Cell Assay |
To evaluate the cellular activity of GNE-7915, cells expressing LRRK2 (such as neuronal cell lines or primary neurons) are seeded in 96-well plates and treated with varying concentrations of GNE-7915. LRRK2-mediated phosphorylation of its substrates (such as Rab10 or Rab12) is assessed by Western blot analysis using phospho-specific antibodies. The EC50 for inhibition of LRRK2 phosphorylation is calculated. Cell viability is monitored to ensure that observed effects are not due to cytotoxicity.
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| Animal Protocol |
Dissolved in 1% methylcellulose in water; 50 mg/kg; i.p. injection and p.o.BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation
The in vivo efficacy of GNE-7915 is evaluated in transgenic mouse models of LRRK2-associated Parkinson's disease, such as LRRK2 G2019S knock-in mice. Mice are administered GNE-7915 orally or intraperitoneally at various doses for a specified period. At the end of the treatment period, animals are euthanized, and brain tissue is collected. LRRK2 substrate phosphorylation in brain lysates is measured by Western blot analysis using phospho-specific antibodies. Dopaminergic neuron integrity can be assessed by immunohistochemical staining for tyrosine hydroxylase. Motor function can be assessed using behavioral tests such as the rotarod test. |
| ADME/Pharmacokinetics |
GNE-7915 tosylate is characterized as being brain-penetrant. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 615.6 and a molecular formula of C26H29F4N5O6S. It is a small molecule with properties suitable for oral administration and central nervous system penetration.
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| Toxicity/Toxicokinetics |
Specific toxicity data for GNE-7915 tosylate are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is a potent and selective LRRK2 inhibitor, and its safety profile would be expected to be consistent with other kinase inhibitors. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
GNE-7915 tosylate is a potent, selective, and brain-penetrant LRRK2 inhibitor with an IC50 of 9 nM. It is used in research related to Parkinson's disease pathogenesis. The compound has a molecular formula of C26H29F4N5O6S and a molecular weight of 615.6. It is supplied for research purposes with a purity of ≥98%.
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| Molecular Formula |
C26H29F4N5O6S
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| Molecular Weight |
615.596978902817
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| Exact Mass |
615.177
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| CAS # |
2070015-00-6
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| Related CAS # |
GNE-7915;1351761-44-8
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| PubChem CID |
78357832
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
42
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| Complexity |
800
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC(C)=CC=1)(O)(=O)=O.N(C1=NC=C(C(F)(F)F)C(NCC)=N1)C1C=C(F)C(C(N2CCOCC2)=O)=CC=1OC
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| InChi Key |
VYAOJDYMEMFZKS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H21F4N5O3.C7H8O3S/c1-3-24-16-12(19(21,22)23)10-25-18(27-16)26-14-9-13(20)11(8-15(14)30-2)17(29)28-4-6-31-7-5-28;1-6-2-4-7(5-3-6)11(8,9)10/h8-10H,3-7H2,1-2H3,(H2,24,25,26,27);2-5H,1H3,(H,8,9,10)
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| Chemical Name |
[4-[[4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-2-fluoro-5-methoxyphenyl]-morpholin-4-ylmethanone;4-methylbenzenesulfonic acid
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| Synonyms |
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.06 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.06 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 of 20% SBE-β-CD physiological saline solution and mix evenly. 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 (4.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6244 mL | 8.1222 mL | 16.2443 mL | |
| 5 mM | 0.3249 mL | 1.6244 mL | 3.2489 mL | |
| 10 mM | 0.1624 mL | 0.8122 mL | 1.6244 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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