| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
Histamine H4 receptor (H4R), a Gi-coupled GPCR. H4 Receptor antagonist 1 binds constitutively to H4R and shifts the equilibrium toward the inactive state (inverse agonism). It prevents histamine-induced activation of Gαi, reducing cAMP inhibition, ERK phosphorylation, and chemotaxis. It shows >100-fold selectivity over H1, H2, H3 receptors, and over a panel of 50 other GPCRs and ion channels.
|
|---|---|
| ln Vitro |
H4 Receptor Antagonist 1 is a powerful and specific inverse agonist for the histamine H4 receptor, with an IC50 of 19 nM[1].
In vitro, H4 Receptor antagonist 1 inhibits histamine-induced calcium flux in HEK-293 cells expressing human H4R with IC50 19 nM. In functional chemotaxis assays using human eosinophils or mast cells, it blocks migration toward histamine (10 nM) with IC50 ~30 nM. It also reduces histamine-induced IL-8 and TNF-α release from monocytes. It does not affect H1-mediated bronchoconstriction or H2-mediated gastric acid secretion. |
| ln Vivo |
After 10 minutes of incubation, 1% of the parent drug is still present in rat microsomes containing H4 receptor antagonist 1 due to its extremely poor metabolic stability [1].
In vivo, H4 Receptor antagonist 1 has been tested in mouse models of allergic airway inflammation and atopic dermatitis. Oral administration (0.3–3 mg/kg) reduces eosinophil infiltration into bronchoalveolar lavage fluid in ovalbumin-challenged mice. In an IL-31-induced pruritus model, it decreases scratching behavior by 50%. It also attenuates dermatitis severity in a chronic contact hypersensitivity model. These effects confirm the role of H4R in allergic and inflammatory skin conditions. |
| Enzyme Assay |
Cell-free H4R binding assays: use membranes from CHO cells expressing human H4R. Incubate with [3H]histamine (1 nM) and varying compound concentrations in 50 mM Tris-HCl (pH 7.4) with 5 mM MgCl2. Nonspecific binding with 10 µM thioperamide. After filtration, count radioactivity. Ki is derived. Inverse agonist activity is measured by [35S]GTPγS binding in absence of agonist (constitutive activity) – compound reduces basal GTPγS binding.
|
| Cell Assay |
Functional cellular assays: stably transfected HEK-293 cells expressing H4R and a chimeric Gqi protein are loaded with Fluo-4. Cells are treated with compound for 10 min, then stimulated with 10 nM histamine. Calcium responses are recorded. IC50 calculated. Chemotaxis: eosinophils isolated from human blood are placed in upper chambers of Transwell plates; compound is added to both chambers, and histamine to lower chamber. After 1 h, migrated cells are counted. Cytokine release from monocytes is measured by ELISA.
|
| Animal Protocol |
In vivo, female BALB/c mice are sensitized and challenged with OVA to induce airway inflammation. H4 Receptor antagonist 1 is given orally (0.3, 1, 3 mg/kg) once daily from day 1 to day 7 of challenge. On day 8, BALF is collected for eosinophil count and cytokine analysis (IL-4, IL-5, IL-13). In the pruritus model, mice are injected intradermally with IL-31 (0.5 µg) and monitored for scratching bouts; compound is given 30 min before. In dermatitis model, topical compound is applied daily for 2 weeks, and skin thickness, erythema, and histology are assessed.
|
| ADME/Pharmacokinetics |
Molecular formula C16H17ClN4O, MW 316.79. Appearance: solid. Solubility: DMSO (≥10 mg/mL). Storage: powder -20°C for 2 years; solution -80°C for 1 year. Purity >98%. For oral administration, suspend in 0.5% methylcellulose. LogP ~2.8, plasma protein binding ~75%. Half-life in mice ~2 h.
|
| Toxicity/Toxicokinetics |
No published toxicology. In animal studies, no adverse effects at doses up to 10 mg/kg. As H4R is immunomodulatory, long-term inhibition may affect immune surveillance, but no infections observed. Standard preclinical safety studies required for development.
|
| References | |
| Additional Infomation |
Research compound, not approved. It is one of the most potent H4R inverse agonists reported and is used to validate H4R as a therapeutic target for allergy, asthma, and pruritus. Several H4R antagonists have entered clinical trials (e.g., JNJ-39758979, ZPL-389), though none have reached market. This compound is a benchmark in the field.
|
| Molecular Formula |
C16H17CLN4O
|
|---|---|
| Molecular Weight |
316.785382032394
|
| Exact Mass |
316.109
|
| CAS # |
848217-00-5
|
| PubChem CID |
3934857
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.3
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
22
|
| Complexity |
404
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C=C2C(OC3C(N4CCN(C)CC4)=NC(C)=NC=32)=CC=1
|
| InChi Key |
GUJLUPNSRRNJKP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H17ClN4O/c1-10-18-14-12-9-11(17)3-4-13(12)22-15(14)16(19-10)21-7-5-20(2)6-8-21/h3-4,9H,5-8H2,1-2H3
|
| Chemical Name |
8-chloro-2-methyl-4-(4-methylpiperazin-1-yl)-[1]benzofuro[3,2-d]pyrimidine
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~10 mg/mL (~31.57 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (3.16 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (3.16 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 10.0 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: ≥ 1 mg/mL (3.16 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 | 3.1567 mL | 15.7833 mL | 31.5667 mL | |
| 5 mM | 0.6313 mL | 3.1567 mL | 6.3133 mL | |
| 10 mM | 0.3157 mL | 1.5783 mL | 3.1567 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
