| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| Other Sizes |
| Targets |
Nav1.7
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| ln Vitro |
AMG8379 exhibits a selectivity that is 100–1000 times greater than that of other members of the NaV family, such as TTX-resistant NaV channels in DRG neurons and NaV1.4 and 1.5 expressed in muscle and the heart, respectively [1]. Based on firing levels in NaV1.7 KO mice, the IC50 for AMG8379's suppression of C-fiber spikes was computed. This value indicates total pharmacological blockage of the NaV1.7 component of the experiment. Accordingly, the IC50 of the AMG8379 module is 47.0 ± 8.1 nM[1].
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| ln Vivo |
AMG8379 (30-100 mg/kg; oral) reduces capsaicin-induced nociceptive responses [1]. In vivo target engagement of AMG8379 in mice was evaluated in multiple NaV1.7-dependent behavioral endpoints. AMG8379 dose-dependently inhibited intradermal histamine-induced scratching and intraplantar capsaicin-induced licking, and reversed UVB radiation skin burn-induced thermal hyperalgesia; notably, behavioral effects were not observed with AMG8380 at similar plasma exposure levels[1].
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| Enzyme Assay |
AMG8379 Antagonist Activity [1]
AMG8379 and AMG8380 represent a pair of atropisomeric quinolone sulfonamides discovered in our efforts to identify an isoform-selective NaV1.7 inhibitor (Fig. 1A). Discovery and optimization of drug-like properties for this chemical class is described in a separate report (Graceffa et al., 2017). AMG8379 potently inhibited recombinant human and mouse, but not rat, NaV1.7 channels expressed in heterologous HEK293 cells when evaluated by automated patch-clamp electrophysiology on a PatchXpress... |
| Animal Protocol |
Animal/Disease Models: CD-1 male mice [1]
Doses: 30 or 100 mg/kg body weight Route of Administration: Oral Experimental Results: There was a dose-dependent reduction in overall nociceptive behavior. |
| References | |
| Additional Infomation |
Highly efficient and selective voltage-gated sodium channel NaV1.7 antagonists offer a promising avenue for developing novel therapies for chronic pain. We synthesized a small-molecule atropine isomer, quinolone sulfonamide antagonist AMG8379, and its less active enantiomer, AMG8380. Using whole-cell patch-clamp electrophysiological experiments with a voltage scheme capable of detecting partially inactivated channels, we demonstrated that AMG8379 effectively blocks human NaV1.7 channels (IC50 8.5 nM) and endogenous tetrodotoxin (TTX)-sensitive sodium channels in dorsal root ganglion (DRG) neurons (IC50 3.1 nM). AMG8379 exhibits 100 to 1000-fold higher selectivity than other NaV family members, including NaV1.4 expressed in muscle and NaV1.5 expressed in the heart, as well as TTX-resistant NaV channels in DRG neurons. In isolated mouse skin-nerve specimens, AMG8379 blocked mechanically stimulated C-fiber action potential firing in a time- and dose-dependent manner. AMG8379 also reduced thermally stimulated C-fiber firing frequency, while AMG8380 had no effect on either mechanical or thermal stimulation. In mice, the targeting effect of AMG8379 was assessed by a variety of NaV1.7-dependent behavioral endpoints. AMG8379 inhibited intradermal histamine-induced scratching and plantar capsaicin-induced licking behaviors in a dose-dependent manner and reversed UVB radiation-induced skin burn hyperalgesia; notably, no behavioral effect was observed with AMG8380 at similar plasma exposure levels. AMG8379 is a potent and selective NaV1.7 inhibitor that blocks sodium currents in heterologous cells and DRG neurons, inhibits action potential firing in peripheral nerve fibers, and has shown pharmacodynamic effects in a conversion model of pruritus and pain. [1]
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| Molecular Formula |
C25H16CLF2N3O5S
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|---|---|
| Molecular Weight |
543.93
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| Exact Mass |
543.046
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| Elemental Analysis |
C, 71.23; H, 4.83; F, 13.00; O, 10.95
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| CAS # |
1641574-26-6
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| Related CAS # |
AMG8379;1642112-31-9;AMG8380;1642112-32-0
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| PubChem CID |
117737142
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| Appearance |
White to off-white solid
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
37
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| Complexity |
969
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1N=C(C=C1)NS(C1C=C2C=CC(=O)N(C3C=C(F)C(C4C=C(F)C=C(Cl)C=4)=CC=3OC)C2=CC=1)(=O)=O
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| InChi Key |
HXQNEKJQBGXFAG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H16ClF2N3O5S/c1-35-23-12-19(15-8-16(26)11-17(27)9-15)20(28)13-22(23)31-21-4-3-18(10-14(21)2-5-25(31)32)37(33,34)30-24-6-7-36-29-24/h2-13H,1H3,(H,29,30)
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| Chemical Name |
1-[4-(3-chloro-5-fluorophenyl)-5-fluoro-2-methoxyphenyl]-N-(1,2-oxazol-3-yl)-2-oxoquinoline-6-sulfonamide
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| Synonyms |
(Rac)AMG8379; AMG8380; (Rac)-AMG8379; AMG8379; 1642112-31-9; 1641574-26-6; AMG 8379; 1-[4-(3-chloro-5-fluorophenyl)-5-fluoro-2-methoxyphenyl]-N-(1,2-oxazol-3-yl)-2-oxoquinoline-6-sulfonamide; 1642112-32-0; (Rac) AMG8379
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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 (~91.9 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (20.8 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 2.08 mg/mL (3.82 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 DMSO stock solution (20.8 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8385 mL | 9.1924 mL | 18.3847 mL | |
| 5 mM | 0.3677 mL | 1.8385 mL | 3.6769 mL | |
| 10 mM | 0.1838 mL | 0.9192 mL | 1.8385 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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