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| 5mg |
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| 25mg |
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| 50mg |
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Purity: ≥98%
GNE-7915 (GNE 7915; GNE7915) is a novel, highly potent, selective, and brain-penetrant leucine-rich repeat kinase 2 (LRRK2) inhibitor with anti-PD (Parkinson's disease) activity. It inhibits LRRK2 with an IC50 and a Ki of 9 nM and 1 nM, respectively. GEN-7915 has been shown to induce dephosphorylation of LRRK2 in the brain of transgenic mice. GNE-7915 is not reported to cause cellular or genetic toxicity, and has progressed into preclinical studies in cynomolgus monkeys. Inhibition of LRRK2 kinase activity has neuroprotective benefits, and provides a means of addressing the underlying biochemical cause of Parkinson's disease for the first time.
| ln Vitro |
For GNE-7915 and compound 19, single-digit nanomolar LRRK2 cell activity was obtained by keeping the methoxy/fluoro arrangement at C-2'/C-5' and varying the aminoalkyl R1 substitutions. Only TTK demonstrated more than 50% inhibition when the Invitrogen kinase assay was expanded to include 0.1 μM (187 kinases) of GNE-7915 (100-fold LRRK2 Ki) and 19 (250-fold LRRK2 Ki). At 0.1 μM, a selectivity analysis of GNE-7915 was conducted utilizing the DiscoverX KinomeScan55 competitive binding assay panel, which comprises 392 distinct kinases. Probe-shift binding was observed at >50% for 10 kinases and >65% exclusively for LRRK2, TTK, and ALK, thereby corroborating GNE-7915's exceptional selectivity for LRRK2. GNE-7915 and 19 only inhibited 5-HT2B, with >70% inhibition at 10 μM, according to cerep receptor analysis (including extended brain panel). In vitro functional tests have demonstrated that GNE-7915 and 19 are moderately potent 5-HT2B antagonists [2].
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| ln Vivo |
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| Animal Protocol |
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| References |
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| Molecular Formula |
C19H21F4N5O3
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|---|---|
| Molecular Weight |
443.40
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| Exact Mass |
443.158
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| CAS # |
1351761-44-8
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| Related CAS # |
GNE-7915 tosylate;2070015-00-6
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| PubChem CID |
58539171
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
629.9±65.0 °C at 760 mmHg
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| Flash Point |
334.7±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.578
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| LogP |
1.81
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
593
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XCFLWTZSJYBCPF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H21F4N5O3/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/h8-10H,3-7H2,1-2H3,(H2,24,25,26,27)
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| Chemical Name |
(4-((4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(morpholino)methanone
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| Synonyms |
GNE 7915; GNE-7915; GNE7915;
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.64 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.
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 (5.64 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 (5.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (5.64 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2553 mL | 11.2765 mL | 22.5530 mL | |
| 5 mM | 0.4511 mL | 2.2553 mL | 4.5106 mL | |
| 10 mM | 0.2255 mL | 1.1276 mL | 2.2553 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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