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| Targets |
SAE-14 targets GPR183 (also known as EBI2), a G protein-coupled receptor involved in immune cell migration and positioning. GPR183 is activated by its endogenous ligand 7α,25-dihydroxycholesterol (7α,25-OHC). By acting as a potent antagonist with an IC50 of 28.5 nM, SAE-14 blocks 7α,25-OHC-induced signaling, including calcium mobilization. This inhibition of GPR183 can modulate immune cell trafficking and inflammatory responses. The compound's ability to reverse allodynia in mice suggests a role for GPR183 in pain pathways, making it a valuable tool for studying neuropathic pain and inflammatory conditions.
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| ln Vitro |
Compound SAE-14, SAE-14, has an IC50 value less than 50 nM and can counteract the calcium mobilization induced by 7α, 25-OHC [1].
In vitro, SAE-14 demonstrates potent antagonism of GPR183 with an IC50 of 28.5 nM in calcium mobilization assays. It effectively inhibits 7α,25-OHC-induced calcium signaling in HL-60 cells with an IC50 below 50 nM. These in vitro data confirm the compound's high potency and specificity for GPR183. The compound's activity is characterized using cell-based calcium flux assays, where the inhibition of the GPR183-mediated calcium response is measured. No specific enzyme inhibition data are reported, as the compound acts at a receptor level. |
| ln Vivo |
In mice with nerve damage, SAE-14 (Compound SAE-14) (once; 2.9 µM; once) reverses allodynia [1].
In vivo, SAE-14 has been shown to reverse nerve injury-induced allodynia in mice. In a study, the compound was administered via the intrathecal (i.th.) route at a dose of 2.9 µM. This single administration was sufficient to reverse the pain hypersensitivity associated with allodynia. This in vivo efficacy demonstrates the potential of GPR183 antagonism in treating neuropathic pain. The compound is being investigated for potential therapeutic applications in conditions where GPR183 signaling contributes to disease pathology. Further in vivo studies are needed to fully characterize its pharmacokinetic and pharmacodynamic profile. |
| Enzyme Assay |
In vitro receptor binding and functional assays for SAE-14 are conducted to characterize its interaction with GPR183. Calcium mobilization assays are performed using cells expressing GPR183, such as HL-60 cells. Cells are loaded with a calcium-sensitive fluorescent dye and stimulated with the agonist 7α,25-OHC in the presence of varying concentrations of SAE-14. The inhibition of the calcium flux is measured, and the IC50 value (28.5 nM) is determined. These assays confirm the compound's potency and antagonistic properties at GPR183.
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| Cell Assay |
Cell Viability Assay [1]
Cell Types: Human Leukemia (HL)-60 Cell Tested Concentrations: 5x Antagonist Incubation Duration: 15 min Experimental Results: GPR183 specific (IC50: 28.5nM) and abolishes 7a, 25-OHC– induction Calcium mobilization in HL-60 cells. In vitro cell-based assays for SAE-14 are conducted using HL-60 cells or other cell lines expressing GPR183. Cells are treated with SAE-14 at various concentrations, typically ranging from sub-nanomolar to micromolar levels, to establish dose-response curves. Calcium mobilization is measured using fluorescent indicators such as Fluo-4 or Fura-2. The inhibition of 7α,25-OHC-induced calcium signaling is the primary readout. These assays confirm the compound's functional antagonism of GPR183 and are used to determine its potency (IC50 < 50 nM). |
| Animal Protocol |
Animal/Disease Models: Male and female ICR mice [1]
Doses: 2.9 µM Route of Administration: intrathecal (i.th.) injection; 2.9 µM; Experimental Results: Reversal of CCI-induced mechanical allodynia in a time-dependent manner. In vivo animal experiments with SAE-14 have been performed in mouse models of neuropathic pain. In one study, SAE-14 was administered intrathecally (i.th.) at a dose of 2.9 µM. The treatment was given once, and its ability to reverse nerve injury-induced allodynia was assessed. Allodynia, a pain response to normally non-painful stimuli, was measured using behavioral tests such as the von Frey filament test. The results demonstrated that SAE-14 effectively reversed the allodynia. These experiments provide proof-of-concept for GPR183 antagonism in pain management. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of SAE-14 are not extensively documented in the available literature. The compound has a molecular weight of 364.36 and a molecular formula of C19H19F3N2O2. It is soluble in DMSO (70 mg/mL). As a small molecule with moderate lipophilicity (due to the trifluoromethyl groups), it is expected to have reasonable oral bioavailability, though specific data are not provided. For in vivo studies, the compound has been administered intrathecally. Storage recommendations are as a powder at -20°C.
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| Toxicity/Toxicokinetics |
Toxicology data for SAE-14 are not extensively reported. The compound is for research use only and is not approved for human therapeutic use. In the in vivo study where it was administered intrathecally to mice at 2.9 µM, no overt toxicity was mentioned. Standard laboratory safety precautions should be followed when handling the compound. The compound should be stored as a powder at -20°C and protected from moisture and light. No specific LD50 or organ toxicity data are available.
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| References | |
| Additional Infomation |
SAE-14 has CAS number 1241280-25-0, molecular formula C19H19F3N2O2, and molecular weight 364.36. It is a potent and specific GPR183 antagonist with an IC50 of 28.5 nM. The compound inhibits 7α,25-OHC-induced calcium mobilization in HL-60 cells with an IC50 below 50 nM. SAE-14 has been shown to reverse nerve injury-induced allodynia in mice. It is being investigated for potential therapeutic applications in cancer, neurodegenerative diseases, and other conditions. Purity is typically 97%. Not approved for clinical use; for research purposes only.
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| Molecular Formula |
C19H19F3N2O2
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| Molecular Weight |
364.3616
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| Exact Mass |
364.139
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| CAS # |
1241280-25-0
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| PubChem CID |
47088557
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| Appearance |
White to off-white solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
462
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1=C([H])C(=C([H])C(=C1[H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H])N([H])C(C([H])([H])C([H])([H])C1C([H])=C([H])C(=C(C=1[H])F)F)=O
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| InChi Key |
SIVJKYRAPQKLIM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H19F3N2O2/c20-14-10-15(12-16(11-14)24-5-7-26-8-6-24)23-19(25)4-2-13-1-3-17(21)18(22)9-13/h1,3,9-12H,2,4-8H2,(H,23,25)
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| Chemical Name |
3-(3,4-difluorophenyl)-N-(3-fluoro-5-morpholin-4-ylphenyl)propanamide
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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 (~274.45 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7445 mL | 13.7227 mL | 27.4454 mL | |
| 5 mM | 0.5489 mL | 2.7445 mL | 5.4891 mL | |
| 10 mM | 0.2745 mL | 1.3723 mL | 2.7445 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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