| Size | Price | Stock | Qty |
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| Targets |
H4R antagonist 1 targets the histamine H4 receptor (H4R), a G-protein-coupled receptor (GPCR) involved in immune cell chemotaxis, cytokine production, and inflammatory responses. The compound exhibits IC₅0 values of 27 nM for human H4R and 290 nM for mouse H4R. It does not show any noticeable binding affinity for other histamine receptor subtypes H1R, H2R, or H3R. The compound is highly selective for H4R over a broad panel of GPCRs, ion channels, and transporters.
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| ln Vitro |
H4R antagonist 1 (compound 48) has been shown to be highly selective for H4R based on competitive binding assays conducted at 10 μM against a wider range of GPCRs, ion channels, and transporters. Compared to human H4R, the inhibitory activity of H4R antagonist 1 on mouse H4R (IC50=0.29 μM) is approximately ten times less potent [1].
In vitro, H4R antagonist 1 shows potent antagonistic activity with an IC₅0 of 27 nM for human H4R. In competitive binding assays against a broad panel of GPCRs, ion channels, and transporters at 10 microM, the compound demonstrates high selectivity for H4R. The inhibitory activity against mouse H4R (IC₅0 = 290 nM) is approximately 10 times weaker than for human H4R. In the GTPgammaS functional assay, H4R antagonist 1 shows inhibitory activity against mouse H4R with an IC₅0 of 690 nM. |
| ln Vivo |
Compound 48, H4R antagonist 1, had noteworthy antipruritic and anti-inflammatory effectiveness in a mouse model produced by oxazolone that resembled human atopic dermatitis (AD) [1]. H4R antagonist 1 demonstrated inhibitory action against mouse H4R in a [35S]GTPγS functional test, with an IC50 of 0.69 μM [1].
In vivo, H4R antagonist 1 demonstrates significant antipruritic and anti-inflammatory efficacy in an oxazolone-induced murine model mimicking human atopic dermatitis (AD). The compound's ability to inhibit H4R-mediated signaling in vivo supports its potential for treating inflammatory skin conditions. The compound shows efficacy in reducing itching and inflammation in preclinical models. Further studies would be needed to characterize its full in vivo pharmacokinetic and efficacy profile. |
| Enzyme Assay |
The in vitro receptor binding assay for H4R antagonist 1 is performed using competitive binding with radiolabeled ligands. Membrane preparations from cells expressing human or mouse H4 receptors are incubated with a radiolabeled H4 receptor ligand (such as [3H]-histamine or [3H]-JNJ7777120) and varying concentrations of the test compound. Bound radioactivity is measured by filtration and scintillation counting. IC₅0 values are calculated from displacement curves. Selectivity is assessed by screening against a panel of related GPCRs, ion channels, and transporters.
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| Cell Assay |
For in vitro cell-based assays, cells expressing human or mouse H4 receptors are cultured and treated with H4R antagonist 1 at various concentrations. Receptor antagonism is measured using functional assays such as GTPgammaS binding (which measures G-protein activation) or calcium mobilization assays (which measure receptor-mediated intracellular calcium flux). IC₅0 values are calculated from dose-response curves. Cells are maintained under standard culture conditions and experiments are typically performed in triplicate.
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| Animal Protocol |
In vivo animal studies for H4R antagonist 1 typically involve murine models of atopic dermatitis or other inflammatory conditions. The oxazolone-induced dermatitis model in mice is commonly used. Mice are sensitized and challenged with oxazolone to induce skin inflammation, then treated with H4R antagonist 1 (typically oral or topical administration). Itching behavior is quantified by counting scratching episodes. Skin inflammation is assessed by measuring ear thickness, histopathological analysis, and inflammatory cytokine levels.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of H4R antagonist 1 are not extensively documented. The compound has molecular weight 335.16 and molecular formula C11H11BrN₈. It is soluble in DMSO and typically formulated for in vitro and in vivo studies. The compound should be stored as powder at -20degC for up to 3 years or in solvent at -80degC for up to 1 year. Shipping is with blue ice or at ambient temperature. Further PK parameters would require dedicated studies.
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| Toxicity/Toxicokinetics |
Toxicological data for H4R antagonist 1 are not well characterized in the public domain. As a research chemical, standard safety precautions should be observed. The compound is for laboratory use only and not intended for human therapeutic applications. H4 receptor antagonists as a class are generally well-tolerated, but comprehensive toxicity profiling would be required for therapeutic development. No significant off-target activity was observed in selectivity screening.
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| References |
[1]. Ko K, et al. Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis. J Med Chem. 2018 Apr 12;61(7):2949-2961.
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| Additional Infomation |
H4R antagonist 1 (CAS# 1429375-54-1) is a highly selective histamine H4 receptor antagonist with molecular formula C11H11BrN₈ and molecular weight 335.16. It has IUPAC name 1-{12-bromo-2,3,4,5,8,10-hexaazatricyclo[7.4.0.02,⁶]trideca-1(9),3,5,7,10,12-hexaen-7-yl}-N-methylazetidin-3-amine. The compound is used in research for anti-itching and anti-inflammation studies and is not approved for clinical use.
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| Molecular Formula |
C11H11BRN8
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| Molecular Weight |
335.162638902664
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| Exact Mass |
334.029
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| CAS # |
1429375-54-1
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| PubChem CID |
71548412
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
0.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
364
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CNC1CN(C1)C2=NC3=C(C=C(C=N3)Br)N4C2=NN=N4
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| InChi Key |
ICGICUHMULRYIQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H11BrN8/c1-13-7-4-19(5-7)10-11-16-17-18-20(11)8-2-6(12)3-14-9(8)15-10/h2-3,7,13H,4-5H2,1H3
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| Chemical Name |
1-(12-bromo-2,3,4,5,8,10-hexazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaen-7-yl)-N-methylazetidin-3-amine
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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 : ~20 mg/mL (~59.67 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (5.97 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 20.0 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 mg/mL (5.97 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 20.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9836 mL | 14.9182 mL | 29.8365 mL | |
| 5 mM | 0.5967 mL | 2.9836 mL | 5.9673 mL | |
| 10 mM | 0.2984 mL | 1.4918 mL | 2.9836 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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