GNE-9605LRRK2 inhibitor, brain-penetrant, potent and selective CAS# 1536200-31-3 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1536200-31-3 | SDF | Download SDF |
| PubChem ID | 76328936 | Appearance | Powder |
| Formula | C17H20ClF4N7O | M.Wt | 449.83 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 60 mg/mL (133.38 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 2-N-[5-chloro-1-[(3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl]pyrazol-4-yl]-4-N-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine | ||
| SMILES | CNC1=NC(=NC=C1C(F)(F)F)NC2=C(N(N=C2)C3CCN(CC3F)C4COC4)Cl | ||
| Standard InChIKey | PUXPEQJKNAWNQA-AAEUAGOBSA-N | ||
| Standard InChI | InChI=1S/C17H20ClF4N7O/c1-23-15-10(17(20,21)22)4-24-16(27-15)26-12-5-25-29(14(12)18)13-2-3-28(6-11(13)19)9-7-30-8-9/h4-5,9,11,13H,2-3,6-8H2,1H3,(H2,23,24,26,27)/t11-,13-/m0/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | GNE-9605 is a highly potent, selective, and brain-penetrant LRRK2 inhibitor with IC50 of 19 nM.
IC50 value:
Target: LRRK2
GNE-9605 retained excellent predicted human metabolic stability when assayed in human liver microsomes and hepatocytes. In
addition, no reversible or time-dependent inhibition of any of the major CYP isoforms was observed. The demonstrated metabolic stability, brain penetration across multiple species, and selectivity of these inhibitors support their use in preclinical efficacy and safety studies. References: | |||||
GNE-9605 Dilution Calculator
GNE-9605 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.2231 mL | 11.1153 mL | 22.2306 mL | 44.4612 mL | 55.5766 mL |
| 5 mM | 0.4446 mL | 2.2231 mL | 4.4461 mL | 8.8922 mL | 11.1153 mL |
| 10 mM | 0.2223 mL | 1.1115 mL | 2.2231 mL | 4.4461 mL | 5.5577 mL |
| 50 mM | 0.0445 mL | 0.2223 mL | 0.4446 mL | 0.8892 mL | 1.1115 mL |
| 100 mM | 0.0222 mL | 0.1112 mL | 0.2223 mL | 0.4446 mL | 0.5558 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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GNE-9605 is a potent and selective inhibitor of LRRK2 with IC50 value of 19 nM [1].
Leucine-rich repeat kinase 2 (LRRK2) is a member of the leucine-rich repeat kinase family. Variants of LRRK2 gene are the most common cause of Parkinson's disease and Crohn's disease.
GNE-9605 is a brain-penetrant, potent and selective LRRK2 inhibitor. GNE-9605 was highly potent against LRRK2 with Ki and IC50 values of 2.0 and 18.7 nM, respectively. In human hepatocytes and liver microsomes, GNE-9605 exhibited excellent human metabolic stability [1].
In rat pharmacokinetic (PK) studies, GNE-9605 exhibited excellent oral bioavailability of 90% and total plasma clearance of 26 mL/min/kg. In bacterial artificial chromosome (BAC) transgenic mice expressing human G2019S LRRK2 protein with the Parkinson’s disease mutation, GNE-9605 (10 or 50 mg/kg) inhibited LRRK2 Ser1292 autophosphorylation with IC50 value of 20 nM in a concentration dependent way. In cynomolgus monkey PK studies, GNE-9605 exhibited excellent brain penetration [1].
Reference:
[1]. Estrada AA, Chan BK, Baker-Glenn C, et al. Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. J Med Chem, 2014, 57(3): 921-936.
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Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors.[Pubmed:24354345]
J Med Chem. 2014 Feb 13;57(3):921-36.
Leucine-rich repeat kinase 2 (LRRK2) has drawn significant interest in the neuroscience research community because it is one of the most compelling targets for a potential disease-modifying Parkinson's disease therapy. Herein, we disclose structurally diverse small molecule inhibitors suitable for assessing the implications of sustained in vivo LRRK2 inhibition. Using previously reported aminopyrazole 2 as a lead molecule, we were able to engineer structural modifications in the solvent-exposed region of the ATP-binding site that significantly improve human hepatocyte stability, rat free brain exposure, and CYP inhibition and induction liabilities. Disciplined application of established optimal CNS design parameters culminated in the rapid identification of GNE-0877 (11) and GNE-9605 (20) as highly potent and selective LRRK2 inhibitors. The demonstrated metabolic stability, brain penetration across multiple species, and selectivity of these inhibitors support their use in preclinical efficacy and safety studies.
