JNJ-7777120

製品コードS2905 バッチS290501

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C14H16ClN3O
分子量 277.75 CAS No. 459168-41-3
Solubility (25°C)* 体外 DMSO 56 mg/mL (201.62 mM)
Ethanol 8 mg/mL (28.8 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 1.500mg/ml (5.40mM) Taking the 1 mL working solution as an example, add 50 μL of 30 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 JNJ-7777120 is the first potent and selective non-imidazole histamine H4 receptor antagonist with Ki of 4.5 nM, exhibits >1000-fold selectivity over the other histamin receptors.
in vitro JNJ 7777120 binds with high affinity to the H4 receptor and has a greater than 1000-fold selectivity over the other histamine receptors. JNJ 7777120 is a selective and potent H4 receptor antagonist with little or no affinity for over 50 other targets. [2]
in vivo JNJ 7777120 has an oral bioavailability of ~30% in rats and 100% in dogs, with a half-life of ∼3 h in both species. JNJ 7777120 blocks histamine-induced chemotaxis and calcium influx in mouse bone marrow-derived mast cells. JNJ 7777120 can block the histamine-induced migration of tracheal mast cells from the connective tissue toward the epithelium in mice. JNJ 7777120 significantly blocks neutrophil infiltration in a mouse zymosan-induced peritonitis model. [2]

プロトコル(参考用のみ)

キナーゼアッセイ Binding assay
Cell pellets from SK-N-MC cells transfected with human, rat, or mouse H4 receptor, human H3 receptor, or human H1 receptor are used. For the mouse H1 receptor binding, fresh mouse brain is used. Cell pellets or mouse brain are homogenized in 50 mM Tris pH 7.5 containing 5 mM EDTA, and supernatants from an 800g spin are collected and recentrifuged at 30,000g for 30 min. Pellets are rehomogenized in 50 mM Tris pH 7.5 containing 5 mM EDTA. For the H4 competition binding studies, human, mouse, and rat cell membranes are incubated with 10, 40, and 150 nM [3H]histamine (specific activity 23 Ci/mmol), respectively, with or without JNJ 7777120 for 45 min at 25°C. Nonspecific binding is defined using 100 μM unlabeled histamine. The Kd values for the human, mouse, and rat H4 receptor are determined to be 5, 42, and 178 nM, respectively, and the Bmax values are determined to be 1.12, 1.7, and 0.68 pmol/mg protein, respectively. Similarly, the ligand used for the H3receptor-binding assays is [3H]N-α-methyl histamine (specific activity, 82 Ci/mmol), and the nonspecific binding is defined using 100 μM unlabeled histamine. The Kd values for the human and rat H3 receptor are determined to be 1 and 0.8 nM, respectively, and the Bmax values are 2.13 and 0.4 pmol/mg protein, respectively. The ligand used for the human and mouse H1 receptor binding is [3H]pyrilamine (specific activity, 20 Ci/mmol), and the nonspecific binding is defined using 10 μM unlabeled diphenhydramine. The Kd is 1 nM for human receptor and 3 nM for the mouse receptor. The Bmax is 2.68 pmol/mg protein for the human receptor and 0.2 pmol/mg protein for the mouse receptor. The binding to the guinea pig H1 and H2 receptors is determined by Cerep, Inc. For the H1 receptor-binding assays, guinea pig cerebellum is used. The radioligand is [3H]pyrilamine, and 100 μM triprolidine is used to determine the nonspecific binding. For the H2 receptor-binding assays, guinea pig striatum is used. The radioligand is [3H]aspartate amino-transferase, and 100 μM tiotidine is used to determine the nonspecific binding. The Kd of [3H]JNJ 7777120 (specific activity, 84 Ci/mmol) for the human and mouse H4 receptor is determined essentially as described above using increasing concentrations of [3H]JNJ 7777120 instead of [3H]histamine in the presence of 100 μM unlabeled histamine. For all studies, the Ki values are calculated based on an experimentally determined appropriate Kd value.
動物実験 動物モデル Female BALB/c mice
投薬量 200 mg/kg
投与方法 P.O.

参考

  • https://pubmed.ncbi.nlm.nih.gov/12954048/
  • https://pubmed.ncbi.nlm.nih.gov/14722321/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

The Host CYP1A1-Microbiota Metabolic Axis Promotes Gut Barrier Disruption in Methicillin-Resistant Staphylococcus aureus-Induced Abdominal Sepsis [ Front Microbiol, 2022, 13:802409] PubMed: 35572636
Effects of Several Therapeutic Agents on Mammalian Vestibular Function: Meclizine, Diazepam, and JNJ7777120 [ J Assoc Res Otolaryngol, 2021, 10.1007/s10162-021-00803-5] PubMed: 34009490
Anteromedial thalamic nucleus to anterior cingulate cortex inputs modulate histaminergic itch sensation. [ Neuropharmacology, 2020, 168:108028] PubMed: 32151646
P-FN12, an H4R-Based Epitope Vaccine Screened by Phage Display, Regulates the Th1/Th2 Balance in Rat Allergic Rhinitis [ Mol Ther Methods Clin Dev, 2018, 11:83-91] PubMed: 30417023
Histamine Regulates the Inflammatory Profile of SOD1-G93A Microglia and the Histaminergic System Is Dysregulated in Amyotrophic Lateral Sclerosis. [ Front Immunol, 2017, 8:1689] PubMed: 29250069
Evidence for a Role of Orexin/Hypocretin System in Vestibular Lesion-Induced Locomotor Abnormalities in Rats [ Front Neurosci, 2016, 10:355] PubMed: 27507932

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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