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Purity: ≥98%
VUF10460 is a non-imidazole agonist of the histamine H4 receptor which binds to rat H4 receptor with a pKi of 7.46. The absence of imidazole heterocycle may have contributed to VUF10460's roughly 50-fold selectivity for the rat H4 receptor compared to the H3 receptor, according to radioligand binding studies. Immethridine and methimepip significantly decreased (by 66% and 48%, respectively) the gastric lesions caused by HCl in conscious rats. Moreover, the H4 receptor agonists VUF10460 and VUF8430 significantly increased the lesions caused by HCl, indicating that the selective agonists' activation of histamine H4 receptors exacerbated the ulcerogenic effects of 0.6 N HCl.
| Targets |
H4 ( pKi = 7.46 )
The target of VUF10460 is the histamine H₄ receptor, and it exhibits approximately a 50-fold selectivity for the rat H₄ receptor over the H₃ receptor. [1] |
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| ln Vitro |
In vitro activity: UF10460 has pKi values of 5.75 and 7.46 for its binding to the rat H3 and H4 receptors, respectively. Rat H4 receptor selectivity over H3 receptor selectivity is roughly 50 times higher in VUF10460[1]. 1. Radioligand binding studies were conducted in HEK 293T cells transfected with either rat histamine H₃ or H₄ receptors to determine the affinity and selectivity of VUF10460. The results showed that VUF10460 had a significantly higher affinity for the rat H₄ receptor compared to the H₃ receptor, with an approximately 50-fold selectivity for the H₄ subtype [1] |
| ln Vivo |
The H4 receptor agonist VUF10460 enhances rat gastric lesions induced by HCl significantly. JNJ7777120, an H4 receptor antagonist, has no effect on this effect [1].
1. In conscious Wistar rats, VUF10460 (as a selective H₄ receptor agonist) significantly enhanced the gastric lesions induced by 0.6N HCl. This proulcerogenic effect was observed, but notably, it was not modified by the H₄ receptor antagonist JNJ7777120 under the experimental conditions [1] |
| Enzyme Assay |
ViF10460 has pKi values of 5.75 and 7.46 for its binding to the rat H3 and H4 receptors, respectively. VUF10460 exhibits a selectivity for the rat H4 receptor that is roughly 50 times greater than that of the H3 receptor. The displacement radioligand binding assay was conducted in a 200 μl total volume of homogenized rat histamine H3 receptor-transfected cells in 50 mM Tris–HCl buffer (pH 7.4 at 25 °C), with or without competing ligands (10− 4 to 10− 11 M). After 60 minutes of incubation at 25 °C, the binding reaction was stopped by quickly filtering through Unifilter GF/C 96-well filterplates (PerkinElmer, USA) that had been pretreated with 0.3% 750 kDa polyethylenimine. This was done three times with ice-cold 50 mM Tris–HCl (pH 7.4 at 4 °C). By using 25 μl of Microscint“O”TM and liquid scintillation counting on the Microbeta Trilux, radioactivity retained on the filter was measured.
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| Cell Assay |
HEK 293 T cells were incubated at 37 °C in a 5% CO2 humidified atmosphere using Dulbeccos modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 50 IU/ml penicillin, and 50 μg/ml streptomycin. Before transfection, about 4 million cells were cultured for an overnight period in a 10-cm dish. To transfect every cell dish, 0.5 ml of serum-free DMEM was used to prepare the transfection mixture. 5 μg of rat histamine H4 or H3 receptor plasmid and 15 μl of 1 mg/ml 25 kDa linear polyethyleneimine (Polyscience, Inc., USA) were added to the mixture, and it was vortexed right away. The mixture was added to the monoloyer cell culture, which was already loaded with 6 ml of fresh cell culture medium, and allowed to incubate for 10 to 15 minutes at room temperature. The cells were scraped off two days after transfection, pelletized by centrifugation, and kept at -20 °C until needed.
1. Radioligand Binding Assay in Transfected HEK 293T Cells: HEK 293T cells were transfected with plasmids encoding rat histamine H₃ or H₄ receptors and cultured under standard cell culture conditions until the receptors were stably expressed on the cell surface. The cells were then incubated with VUF10460 at different concentrations along with a radiolabeled histamine receptor ligand. After incubation, unbound ligands were removed by washing, and the radioactivity associated with the cells was measured to quantify the binding affinity of VUF10460 for H₃ and H₄ receptors. The selectivity of VUF10460 for the H₄ receptor over H₃ was calculated based on the binding data [1] |
| Animal Protocol |
Rats: VUF10460 is dissolved in 100% DMSO. Rats that have been fasted for 24 hours are given 0.6 N HCl (5 mL/kg volume) intragastrically to cause gastric lesions. Subcutaneous administration of study drugs occurs 30 minutes prior to HCl. Randomly selected rats are given single doses (10 and/or 30 mg/kg) of the vehicle, VUF8430, VUF10460, methimepip, immepip, or VUF8430 in a volume of 1 mL/kg[1].
1. Gastric Lesion Induction and Drug Treatment in Rats: Male Wistar rats were used as experimental animals and were kept under standard laboratory conditions with free access to food and water before the experiment. VUF10460 was prepared in a suitable vehicle (the specific formulation was not detailed in the literature) and administered to the rats via an unspecified route at a certain dose prior to the challenge with 0.6N HCl. The HCl was administered intragastrically to induce gastric mucosal lesions. After a specified period (the incubation time was not detailed), the rats were sacrificed, and their stomachs were excised to evaluate the extent of gastric lesions by measuring the lesion area or score. For the antagonist intervention group, JNJ7777120 was administered before VUF10460 to observe whether it could reverse the proulcerogenic effect of VUF10460 [1] |
| References | |
| Additional Infomation |
1. VUF10460 is a selective rat histamine H₄ receptor agonist with a selectivity for H₄ receptors that is about 50 times higher than that for H₃ receptors. It has a pro-ulceration effect on hydrochloric acid-induced gastric injury in rats, suggesting that H₄ receptors may play a role in gastric mucosal homeostasis, but the exact mechanism is unclear because the H₄ receptor antagonist JNJ7777120 did not block this effect [1]. 2. This study highlights the species-dependent differences in affinity and selectivity of histaminergic ligands (such as VUF10460), and these differences need to be considered when pharmacologically characterizing the function of histamine H₃ and H₄ receptors in vivo [1].
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| Molecular Formula |
C₁₅H₁₉N₅
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| Molecular Weight |
269.34
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| Exact Mass |
269.164
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| Elemental Analysis |
C, 66.89; H, 7.11; N, 26.00
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| CAS # |
1028327-66-3
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| Related CAS # |
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| PubChem CID |
25129523
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
523.8±60.0 °C at 760 mmHg
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| Flash Point |
270.6±32.9 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.621
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| LogP |
1.27
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
297
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1C=CC(C2=CC(=NC(N)=N2)N2CCN(C)CC2)=CC=1
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| InChi Key |
NIJGWJIOMPHDBP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H19N5/c1-19-7-9-20(10-8-19)14-11-13(17-15(16)18-14)12-5-3-2-4-6-12/h2-6,11H,7-10H2,1H3,(H2,16,17,18)
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| Chemical Name |
4-(4-methylpiperazin-1-yl)-6-phenylpyrimidin-2-amine
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.28 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 (9.28 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 (9.28 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 | 3.7128 mL | 18.5639 mL | 37.1278 mL | |
| 5 mM | 0.7426 mL | 3.7128 mL | 7.4256 mL | |
| 10 mM | 0.3713 mL | 1.8564 mL | 3.7128 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.
Effects of the selective histamine H4receptor agonists VUF8430 (30mg/kg) and VUF10460 (10mg/kg) on the gastric lesions induced by 0.6N HCl (5ml/kg, Vehicle), in the absence (A) or in the presence (B) of the selective histamine H4receptor antagonist JNJ7777120 (10mg/kg).Eur J Pharmacol.2011 Nov 1;669(1-3):121-7. |
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n the top (A), macroscopic aspects of gastric mucosa from rats treated with Vehicle (saline, 1ml/kg), Vehicle±0.6N HCl (5ml/kg) or immethridine (30mg/kg)+0.6N HCl. On the bottom, effects of immethridine (10mg/kg, B), immethridine (30mg/kg, C) or methimepip (30mg/kg, D) on the gastric ulcerogenic response to 0.6N HCl (Vehicle).Eur J Pharmacol.2011 Nov 1;669(1-3):121-7. |
Effect of the selective histamine H3receptor agonist immethridine (30mg/kg) on the gastric lesions induced by 0.6N HCl (5ml/kg, Vehicle) in the absence or in the presence of the selective histamine H3receptor antagonist A-331440 (30mg/kg, A) or the selective histamine H4receptor antagonist JNJ7777120 (10mg/kg, B).Eur J Pharmacol.2011 Nov 1;669(1-3):121-7. |
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