| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| Other Sizes |
| Targets |
MrgprX2[1]
Targets MrgprX2 (MAS-related GPR family member X2) as a selective antagonist. MrgprX2 is a GPCR expressed primarily on mast cells, sensory neurons, and keratinocytes. Activation of MrgprX2 by cationic basic substances (e.g., substance P, cortistatin, many FDA-approved drugs) triggers mast cell degranulation, leading to pseudo-allergic reactions, itch, and inflammatory responses. |
|---|---|
| ln Vitro |
A member of the Mas-related gene family, MRGPRX2 has been shown to express itself in mast cells, sensory neurons, and, more recently, keratinocytes. Adipose tissue, the esophagus, the bladder, the lung, and the skin contain the highest levels of MRGPRX2 mRNA. Mast cell degranulation and consequent pseudoallergic responses are caused by activation of MRGPRX2 [2].
In vitro, MrgprX2 antagonist-1 potently inhibits MrgprX2-mediated signaling, blocking mast cell degranulation in response to MrgprX2 agonists. Activation of MRGPRX2 leads to mast cell degranulation with subsequent pseudo-allergic reactions. This antagonist prevents these effects, thereby reducing the release of inflammatory mediators such as histamine, tryptase, and pro-inflammatory cytokines from mast cells. |
| ln Vivo |
In vivo activity data for MrgprX2 antagonist-1 is not publicly available. As an MrgprX2 antagonist, it has potential applications in animal models of skin inflammatory disorders, including contact dermatitis, atopic dermatitis, and urticaria. By blocking MrgprX2, it could reduce mast cell-mediated inflammation, itch, and vascular permeability. However, no published animal studies are available.
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| Enzyme Assay |
Cell-free radioligand binding assays for MrgprX2 are performed using membranes from MrgprX2-transfected HEK293 cells. Membranes (10-20 microg/well) are incubated with a radiolabeled MrgprX2 agonist (e.g., [3H]substance P or [¹2⁵I]-labeled compound) and increasing antagonist concentrations (0.1 nM-10 microM) in binding buffer for 60 min at 25degC. Bound radioactivity is separated by filtration and counted. Detailed assay protocols specific to this compound are not publicly available.
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| Cell Assay |
Functional assays are performed using LAD2 human mast cells or RBL-2H3 cells expressing MrgprX2. Cells are seeded in 96-well plates and pre-incubated with MrgprX2 antagonist-1 (0.1 nM-10 microM) for 30 min at 37degC. Cells are then stimulated with an MrgprX2 agonist (e.g., substance P, 10 microM, or compound 48/80, 3 microg/mL) for 30 min. Mast cell degranulation is measured by beta-hexosaminidase release assay (substrate 4-nitrophenyl N-acetyl-beta-D-glucosaminide). Histamine release is measured by ELISA. Inhibition of mediator release is calculated.
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| Animal Protocol |
No specific animal studies have been reported for MrgprX2 antagonist-1. For an MrgprX2 antagonist, potential in vivo models include mouse models of contact dermatitis (oxazolone- or DNFB-induced), passive cutaneous anaphylaxis (PCA), or compound 48/80-induced mast cell-dependent inflammation. MrgprX2 antagonist-1 would be administered topically or systemically (i.p., 1-30 mg/kg) prior to challenge, with endpoints including ear swelling, vascular permeability (Evans blue dye extravasation), mast cell degranulation (histology), and inflammatory cytokine levels.
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| ADME/Pharmacokinetics |
Detailed PK data for MrgprX2 antagonist-1 is not publicly available. As a small molecule (MW 410.36, C1₅H1₅F₅N4O2S), its pharmacokinetic properties are not reported. Solubility information is limited. For skin inflammatory disorders, topical administration could be a viable route to achieve local exposure while minimizing systemic toxicity. However, specific PK parameters have not been published.
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| Toxicity/Toxicokinetics |
No toxicity data is publicly available for MrgprX2 antagonist-1. As a selective antagonist of MrgprX2, which is primarily involved in pseudo-allergic reactions, its inhibition is not expected to cause significant toxicity. However, MrgprX2 also plays roles in host defense (antimicrobial peptide sensing) and wound healing, so long-term antagonism could theoretically affect these processes. Standard toxicity studies would be required for development.
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| References | |
| Additional Infomation |
MrgprX2 antagonist-1 is a research chemical not approved for clinical use. It is a valuable tool for studying MrgprX2 biology, which has emerged as an important mediator of pseudo-allergic drug reactions, contact dermatitis, chronic urticaria, atopic dermatitis, and other mast cell-driven inflammatory skin disorders. This compound is particularly useful for identifying whether MrgprX2 is responsible for specific mast cell responses in various pathological contexts.
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| Molecular Formula |
C15H15F5N4O2S
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|---|---|
| Molecular Weight |
410.36221909523
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| Exact Mass |
410.083
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| CAS # |
2642162-06-7
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| PubChem CID |
162641702
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| Appearance |
White to light yellow solid powder
|
| LogP |
2.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
491
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S1C(CC2C=C(C=C(C=2)F)F)=NN=C1NC(N(CC)C[C@H](C(F)(F)F)O)=O
|
| InChi Key |
QJCRGWUNWPWJCQ-LLVKDONJSA-N
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| InChi Code |
InChI=1S/C15H15F5N4O2S/c1-2-24(7-11(25)15(18,19)20)14(26)21-13-23-22-12(27-13)5-8-3-9(16)6-10(17)4-8/h3-4,6,11,25H,2,5,7H2,1H3,(H,21,23,26)/t11-/m1/s1
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| Chemical Name |
3-[5-[(3,5-difluorophenyl)methyl]-1,3,4-thiadiazol-2-yl]-1-ethyl-1-[(2R)-3,3,3-trifluoro-2-hydroxypropyl]urea
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 66.67 mg/mL (162.47 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.09 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 (6.09 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 (6.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4369 mL | 12.1844 mL | 24.3688 mL | |
| 5 mM | 0.4874 mL | 2.4369 mL | 4.8738 mL | |
| 10 mM | 0.2437 mL | 1.2184 mL | 2.4369 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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