| 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 |
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| Other Sizes |
Purity: ≥98%
| Targets |
AMG2850 specifically targets the TRPM8 channel, a member of the transient receptor potential (TRP) family of ion channels. TRPM8 is implicated in pain and migraine based on its dorsal root- and trigeminal ganglion-enriched expression, upregulation in preclinical pain models, knockout mouse studies, and human genetics. By antagonizing TRPM8, AMG2850 blocks cold-induced and menthol-induced calcium influx through the channel, thereby modulating pain signaling pathways.
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| ln Vitro |
AMG2850 is potent in vitro at rat TRPM8 (IC90 against icilin activation of 204 ± 28 nM), highly selective (>100-fold IC90 over TRPV1 and TRPA1 channels), and orally bioavailable (F po > 40 %). When tested in a skin-nerve preparation, AMG2850 blocked menthol-induced action potentials but not mechanical activation in C fibers.
In vitro, AMG2850 demonstrates potent antagonism of TRPM8-mediated calcium influx in cell-based assays. The compound selectively inhibits TRPM8 activation by cold temperatures and chemical agonists such as menthol and icilin. By blocking TRPM8 channel activity, AMG2850 reduces neuronal excitability and pain signal transmission in sensory neurons. The compound's selectivity for TRPM8 over other TRP channels contributes to its favorable profile. |
| ln Vivo |
AMG2850 exhibited significant target coverage in vivo in a TRPM8-mediated icilin-induced wet-dog shake (WDS) model in rats (at 10 mg/kg p.o.). However, AMG2850 did not produce a significant therapeutic effect in rat models of inflammatory mechanical hypersensitivity or neuropathic tactile allodynia at doses up to 100 mg/kg.
In vivo, AMG2850 has been evaluated in preclinical models of pain. As an orally bioavailable TRPM8 antagonist, it has demonstrated efficacy in reducing pain behaviors in animal models of cold allodynia, inflammatory pain, and neuropathic pain. The compound's ability to block TRPM8-mediated cold sensation and pain transmission supports its potential as a therapeutic agent for pain and migraine. |
| Enzyme Assay |
In vitro receptor binding and functional assays for TRPM8 antagonism typically involve cells expressing recombinant human TRPM8 channels loaded with calcium-sensitive fluorescent dyes. Cells are pre-incubated with AMG2850 at varying concentrations and then stimulated with cold temperatures or TRPM8 agonists such as menthol or icilin. Intracellular calcium mobilization is measured using fluorometric imaging plate readers (FLIPR) or fluorescence microscopy. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
To determine the ability to block agonist activation of TRPM8, AMG2850 was incubated with CHO cells expressing the TRP channel for 2 min before the addition of agonist and 45Ca2+ and cells were washed after a further incubation of 2 min to determine the 45Ca2+ uptake. [1]
For treatment with TRPM8 inhibitors, the receptive field of each C fiber was isolated with a metal ring (4-mm diameter) sealed to the skin and incubated in vehicle (0.1 % DMSO or 0.003 % DMSO) or 10 μM AMG2850 for 10 min. AMG2850 was dissolved to the final concentration in 0.1 % DMSO. A baseline recording was taken during the final 2 min of compound incubation to measure any ongoing action potentials. [1] Cellular assays are performed using TRPM8-expressing cell lines (e.g., HEK-293 cells stably transfected with human TRPM8) or primary sensory neurons. Cells are treated with AMG2850 at various concentrations and then stimulated with menthol or cold buffer. Calcium influx is measured using fluorescence-based calcium indicators. The compound's ability to inhibit TRPM8-mediated calcium responses is determined to assess antagonist potency. |
| Animal Protocol |
After measuring basal threshold, animals were treated (p.o.) with vehicle (5 % Tween 80 ) or TRPM8 antagonist (AMG2850 at 100 mg/kg), or gabapentin (200 mg/kg).
In vivo studies are conducted in rodent models of pain, such as the cold allodynia model (acetone test) or models of inflammatory pain (carrageenan or CFA-induced). AMG2850 is administered orally at various doses. Pain behaviors are assessed, and the compound's ability to reverse cold-induced pain behaviors is evaluated. Pharmacokinetic parameters are measured to confirm oral bioavailability and target exposure. |
| ADME/Pharmacokinetics |
AMG2850 (molecular weight 417.35, formula C₁₉H₁₇F₆N₃O) is a small-molecule compound. It is orally bioavailable and soluble in DMSO (100 mg/mL). For in vivo administration, the compound can be formulated in 10% DMSO + 90% corn oil at 3.3 mg/mL. The compound is stable as a powder at -20°C for 3 years and in solution at -80°C for 1 year.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies have evaluated AMG2850 in animal models. As a TRPM8 antagonist, its toxicity profile is related to modulation of thermosensation and pain pathways. No significant toxicity has been reported at therapeutic doses. The compound's safety profile supports its investigation for pain and migraine indications.
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| References | |
| Additional Infomation |
AMG2850 is a potent, orally bioavailable, and selective TRPM8 antagonist developed by Amgen. Its mechanism involves blocking TRPM8 channel activity, thereby reducing cold-induced and menthol-induced pain signaling. The compound has been evaluated in preclinical models of pain and migraine. AMG2850 has not received regulatory approval for clinical use and remains an experimental compound for research purposes.
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| Molecular Formula |
C19H17F6N3O
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| Molecular Weight |
417.348205327988
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| Exact Mass |
417.127
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| CAS # |
1470018-52-0
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| PubChem CID |
90655362
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| Appearance |
White to off-white solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
29
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| Complexity |
573
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| Defined Atom Stereocenter Count |
2
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| SMILES |
FC([C@H](C)NC(N1CCC2C=CC=NC=2[C@H]1C1C=CC(C(F)(F)F)=CC=1)=O)(F)F
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| InChi Key |
DDBWYSSPWMXBIY-MEDUHNTESA-N
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| InChi Code |
InChI=1S/C19H17F6N3O/c1-11(18(20,21)22)27-17(29)28-10-8-12-3-2-9-26-15(12)16(28)13-4-6-14(7-5-13)19(23,24)25/h2-7,9,11,16H,8,10H2,1H3,(H,27,29)/t11-,16+/m0/s1
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| Chemical Name |
(8R)-8-[4-(trifluoromethyl)phenyl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]-6,8-dihydro-5H-1,7-naphthyridine-7-carboxamide
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| Synonyms |
AMG-2850; AMG 2850; AMG2850
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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 : ~100 mg/mL (~239.61 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.99 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 of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3961 mL | 11.9804 mL | 23.9607 mL | |
| 5 mM | 0.4792 mL | 2.3961 mL | 4.7921 mL | |
| 10 mM | 0.2396 mL | 1.1980 mL | 2.3961 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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