| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
The primary target of Adriforant hydrochloride is the histamine H4 receptor (H4R), a G protein-coupled receptor that plays a key role in immune cell chemotaxis and inflammatory responses. The compound acts as a potent H4 receptor antagonist with a binding affinity Ki of 2.4 nM and a functional antagonist Ki of 1.56 nM. By blocking H4 receptor activation, Adriforant hydrochloride inhibits histamine-induced immune cell activation, including eosinophil shape change, CD11b upregulation, and actin polymerization. The H4 receptor is a validated target for inflammatory and allergic diseases, making this compound a valuable research tool.
|
|---|---|
| ln Vitro |
Based on functional assay data, convergent predictions of effective free plasma concentrations and rapid on/fast off of rhH4R by Adriforant were observed when the compound was tested and observed for H4R, with binding Ki=2.4 nM and functional Ki=1.56 nM (compound 13). Actin polymerization is measured in vitro using natively isolated human eosinophils, and the IC50 is 1.16 nM. The suggested concentration is 12 nM if it is assumed that 10-fold the IC50 is needed to achieve >90% receptor occupancy (and thus almost complete inhibition of the response). The whole blood GAFS assay data show that at a total blood concentration of 30 nM (corrected for PPB and blood partitioning equivalent to approximately 10 nM free), imetit-induced shape changes are completely blocked. Ceff/Cmin concentrations between 10–15 nM are utilized for safety margin computations and dose prediction [1].
In vitro studies demonstrate that Adriforant hydrochloride is a potent H4 receptor antagonist with a binding affinity Ki of 2.4 nM and a functional antagonist Ki of 1.56 nM. The compound effectively prevents histamine-induced shape change, CD11b protein upregulation, and actin polymerization in isolated human eosinophils with IC₅0 values of 0.65, 4.9, and 1.3 nM, respectively. These potent inhibitory effects on eosinophil activation make Adriforant hydrochloride a valuable tool for studying H4 receptor biology and its role in allergic and inflammatory diseases. The compound's selectivity for H4 over other histamine receptors is a key feature of its activity profile. |
| ln Vivo |
In vivo studies of Adriforant hydrochloride are focused on evaluating its efficacy in animal models of allergic and inflammatory diseases. As an orally bioavailable H4 receptor antagonist with potent in vitro activity, the compound is expected to demonstrate significant therapeutic effects in vivo. Adriforant hydrochloride may be used to study the role of H4 receptors in conditions such as asthma, allergic rhinitis, atopic dermatitis, and pruritus. Further in vivo studies are needed to fully characterize its pharmacokinetic properties, bioavailability, and efficacy in various disease models. The compound's oral bioavailability supports its use in oral administration studies.
|
| Enzyme Assay |
For in vitro enzyme/receptor binding assays, Adriforant hydrochloride can be evaluated using radioligand binding studies with membranes expressing the human histamine H4 receptor. Competition binding experiments using a labeled H4 receptor ligand can determine the compound's affinity (Ki) for the receptor. Functional antagonist activity is assessed using cell-based assays that measure H4 receptor-mediated signaling, such as calcium mobilization, cAMP inhibition, or chemotaxis assays. Dose-response curves are generated to determine IC₅0 values for functional antagonism. Standard assay conditions include physiological buffer systems with appropriate pH and ionic strength.
|
| Cell Assay |
For in vitro cellular experiments, Adriforant hydrochloride is typically tested in cells expressing the H4 receptor, such as human eosinophils, mast cells, or cell lines transfected with H4R. Cells are cultured in appropriate media and treated with various concentrations of the compound (typically ranging from picomolar to micromolar) in the presence or absence of histamine. Receptor activation is measured by assessing eosinophil shape change, CD11b upregulation, actin polymerization, or other activation markers. Chemotaxis assays can be used to measure H4-mediated cell migration. Signaling pathway activation is assessed by measuring calcium flux or cAMP levels.
|
| Animal Protocol |
For in vivo animal experiments, Adriforant hydrochloride can be administered to rodents via oral gavage, taking advantage of its oral bioavailability. The compound can be evaluated in models of allergic inflammation, such as ovalbumin-induced asthma, passive cutaneous anaphylaxis, or models of pruritus. Typical dosing regimens may range from 0.1 to 10 mg/kg depending on the study objectives. Inflammatory markers, immune cell infiltration, and disease severity are assessed. Pharmacodynamic markers such as H4 receptor occupancy or downstream signaling can be measured. Animal studies should follow appropriate ethical guidelines.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Adriforant hydrochloride include oral bioavailability, supporting its administration via oral gavage in vivo. As a small molecule with a molecular weight of 371.74 g/mol, it is likely to have reasonable absorption and distribution characteristics. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's metabolism, potential for drug-drug interactions, and excretion pathways remain to be fully characterized. The compound's trihydrochloride salt form may influence its solubility and stability.
|
| Toxicity/Toxicokinetics |
Toxicological data for Adriforant hydrochloride are limited, as it is primarily a research tool. As an H4 receptor antagonist, its toxicity would depend on the importance of H4 receptors for normal immune function. H4 receptors are involved in immune cell chemotaxis and inflammatory responses, and their inhibition could have immunomodulatory effects. Comprehensive toxicology studies including acute and repeated-dose toxicity, genotoxicity, and cardiotoxicity assessments would be needed for further development. Appropriate safety precautions should be taken when handling this compound, including the use of personal protective equipment and adherence to institutional safety guidelines.
|
| References | |
| Additional Infomation |
Adriforant hydrochloride is a research compound used to study H4 receptor biology and develop therapies for allergic and inflammatory diseases. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a novel histamine H4 receptor antagonist with a binding affinity Ki of 2.4 nM and a functional antagonist Ki of 1.56 nM. It prevents histamine-induced eosinophil activation with IC₅0 values of 0.65, 4.9, and 1.3 nM and is orally bioavailable.
|
| Molecular Formula |
C13H25CLN6O
|
|---|---|
| Molecular Weight |
316.830200910568
|
| Exact Mass |
370.12
|
| CAS # |
2096455-90-0
|
| PubChem CID |
131801117
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
22
|
| Complexity |
295
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
N([C@@H]1CCN(C2=NC(N)=NC(NCC3CC3)=C2)C1)C.Cl.O
|
| InChi Key |
ZAZAFXLCZSALFI-FYBBWCNBSA-N
|
| InChi Code |
InChI=1S/C13H22N6.3ClH/c1-15-10-4-5-19(8-10)12-6-11(17-13(14)18-12)16-7-9-2-3-9;;;/h6,9-10,15H,2-5,7-8H2,1H3,(H3,14,16,17,18);3*1H/t10-;;;/m1.../s1
|
| Chemical Name |
4-N-(cyclopropylmethyl)-6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyrimidine-2,4-diamine;trihydrochloride
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ~100 mg/mL (~269.01 mM)
DMSO : ≥ 83.33 mg/mL (~224.16 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (269.01 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1563 mL | 15.7813 mL | 31.5627 mL | |
| 5 mM | 0.6313 mL | 3.1563 mL | 6.3125 mL | |
| 10 mM | 0.3156 mL | 1.5781 mL | 3.1563 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
