| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Toreforant targets the histamine H4 receptor (H4R), a G protein-coupled receptor that is predominantly expressed on immune cells, including eosinophils, mast cells, basophils, and T cells. The H4 receptor plays a key role in mediating histamine-induced chemotaxis of immune cells and the release of pro-inflammatory cytokines. Activation of H4R by histamine promotes the recruitment and activation of immune cells at sites of inflammation, contributing to allergic and inflammatory responses. Toreforant is a selective H4R antagonist with a Ki of 8.4 nM at the human receptor. It shows excellent selectivity over other receptors including the other histamine receptors (H1, H2, H3). By blocking H4R activation, Toreforant inhibits histamine-induced immune cell chemotaxis and cytokine release.
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| ln Vitro |
Toreforant works as an antagonist of human H4R in human polymorphonuclear leukocytes by inhibiting histamine-induced shape alterations in human eosinophils and shifting the histamine dose-response curve to the right. Since this measurement is not in equilibrium, pA2 must be calculated carefully. The change in the antagonist's minimum concentration can be used to determine pA2. The resulting pA2 was roughly 7.5, which agreed with the transfection system's findings. Toreforant reduces the effects of histamine in isolated cells, and the experiment may also be run on whole blood. The IC50 values were 296 nM and 780 nM, respectively, when employing 100 nM and 300 nM histamine[1].
Toreforant demonstrates potent in vitro activity as a histamine H4 receptor antagonist. The compound has a Ki of 8.4 nM at the human H4 receptor and shows excellent selectivity over other receptors, including the other histamine receptors. Toreforant works as an antagonist of human H4R in human polymorphonuclear leukocytes by inhibiting histamine-induced shape alterations in human eosinophils and shifting the histamine dose-response curve to the right. These findings confirm the compound's mechanism of action as a selective H4 receptor antagonist. The compound's potent and selective H4R antagonism makes it a valuable tool for studying H4 receptor function in immune responses and inflammation. |
| ln Vivo |
The animals administered 100 mg/kg of toreforant exhibited a decrease in illness severity scores. The score decrease is comparable to that of JNJ 28307474. Toreforant's anti-itching efficacy was assessed using the histamine-induced CD-1 mouse scratching paradigm (n = 5 per group). In contrast to other H4R antagonists, toreforant does not effectively lessen itching caused by histamine. After oral administration to rats, toreforant produced radioactivity that was widely distributed into tissues; however, it was not quantifiable in the medulla, spinal cord, cerebellum, or cerebrum of either Sprague Dawley or Long Evans rats, suggesting that drug-derived radioactivity does not cross the blood-brain barrier. Toreforant and JNJ 39758979, an H4R antagonist that can pass the blood-brain barrier, were used to create a rat neuropathic pain model. Toreforant produced no activity, but JNJ 39758979 was able to dramatically reduce mechanical allodynia induced in a rat spinal nerve ligation model [1].
Toreforant is an investigational compound that has been evaluated in clinical trials for inflammatory and autoimmune conditions, including rheumatoid arthritis. The compound is orally active, making it suitable for oral administration in clinical studies. In preclinical and clinical studies, Toreforant has been evaluated for its ability to inhibit H4R-mediated inflammatory responses. The compound's selectivity for H4R over other histamine receptors supports its potential for treating inflammatory diseases with reduced side effects. Detailed in vivo efficacy data, including specific clinical trial results, are available in the published literature. Toreforant is a valuable tool for studying the role of H4 receptors in inflammation and for evaluating H4 receptor antagonists as therapeutic agents. |
| Enzyme Assay |
The in vitro receptor binding assay for Toreforant measures the binding affinity of the compound to the histamine H4 receptor. Membrane preparations from cells expressing the human H4 receptor are incubated with varying concentrations of Toreforant (typically ranging from nanomolar to micromolar) in the presence of a radiolabeled H4 receptor ligand. The amount of bound radioligand is measured by scintillation counting, and Ki values are determined by fitting competition binding curves. The Ki value of 8.4 nM is determined for the human H4 receptor. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. Selectivity is assessed by testing the compound against other histamine receptors (H1, H2, H3) and other receptor classes. Appropriate positive controls (known H4 antagonists) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
The in vitro cellular functional assay for Toreforant measures the compound's ability to antagonize H4 receptor-mediated signaling in human immune cells. Human polymorphonuclear leukocytes or eosinophils are treated with varying concentrations of Toreforant or vehicle control (DMSO) prior to stimulation with histamine. H4 receptor activation is assessed by measuring histamine-induced shape alterations in eosinophils or by measuring chemotaxis. The inhibition of these responses by Toreforant is quantified, and antagonist potency is determined. The compound's ability to shift the histamine dose-response curve to the right is also assessed. The compound's effects on cytokine release from immune cells can also be measured.
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| Animal Protocol |
In vivo animal experiments with Toreforant are conducted using rodent models of inflammatory diseases, such as allergic airway inflammation, contact hypersensitivity, or rheumatoid arthritis models. Toreforant is administered orally at various doses due to its oral bioavailability. Inflammatory endpoints such as immune cell infiltration, cytokine levels, and tissue pathology are measured. The compound's anti-inflammatory efficacy is evaluated by comparing disease severity in treated versus control groups. Toreforant has also been evaluated in clinical trials for rheumatoid arthritis. Detailed experimental protocols, including dosing regimens and endpoints, are described in the primary literature and clinical trial reports.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for Toreforant are not extensively documented in publicly available sources. The compound is orally active. Toreforant has a molecular weight of approximately 360.45 and a chemical formula of C19H25FN4O (free base). The compound is soluble in DMSO for formulation purposes. For in vivo oral administration, Toreforant is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and clinical trial reports and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for Toreforant are available from preclinical and clinical studies conducted during its development for inflammatory conditions. As a research-grade compound, Toreforant is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Toxicological data from preclinical and clinical studies are available in the published literature and should be consulted for safety information.
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| References | |
| Additional Infomation |
Toreforant has been used in trials investigating its use to treat asthma, psoriasis, liver dysfunction, and rheumatoid arthritis.
Toreforant is a research compound developed for studying the role of the histamine H4 receptor in inflammation and for evaluating H4 receptor antagonists as therapeutic agents for inflammatory and autoimmune diseases. The compound is also known as JNJ-38518168. Toreforant is a small-molecule, orally active, and selective antagonist of the H4 receptor with a Ki of 8.4 nM at the human receptor and excellent selectivity over other receptors. The compound has been evaluated in clinical trials for rheumatoid arthritis. Toreforant is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical research. Toreforant is available from various chemical suppliers for research purposes. Its utility lies in its ability to selectively antagonize H4 receptors and probe their role in inflammation and immune responses. |
| Molecular Formula |
C23H32N6
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|---|---|
| Molecular Weight |
392.540384292603
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| Exact Mass |
392.268
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| CAS # |
952494-46-1
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| PubChem CID |
23650961
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
611.2±65.0 °C at 760 mmHg
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| Flash Point |
323.4±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.621
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| LogP |
4.22
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
508
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
FCRFVPZAXGJLPW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H32N6/c1-15-12-16(2)21-20(13-15)27-22(28-21)19-14-25-23(26-17(19)3)24-9-5-6-18-7-10-29(4)11-8-18/h12-14,18H,5-11H2,1-4H3,(H,27,28)(H,24,25,26)
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| Chemical Name |
5-(4,6-dimethyl-1H-benzimidazol-2-yl)-4-methyl- N-[3-(1-methylpiperidin-4-yl)propyl]pyrimidin-2-amine
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| Synonyms |
JNJ-38518168; JNJ 38518168; JNJ38518168
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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 : ~100 mg/mL (~254.75 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.37 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 (6.37 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 (6.37 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 | 2.5475 mL | 12.7376 mL | 25.4751 mL | |
| 5 mM | 0.5095 mL | 2.5475 mL | 5.0950 mL | |
| 10 mM | 0.2548 mL | 1.2738 mL | 2.5475 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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