JNJ-7777120是一种强效的和具有选择性的组胺 H4受体拮抗剂 (Ki=4.5 nM)。JNJ-7777120 能有效阻断组胺诱导的小鼠气管肥大细胞从结缔组织向上皮细胞的迁移。JNJ-7777120 还能在小鼠 Zymosan 诱导的腹膜炎模型中显著阻断中性粒细胞的浸润。JNJ-7777120 具有研究抗瘙痒和抗炎的较好潜力。
| 生物活性 | JNJ-7777120 is a potent and selectivehistamineH4receptorantagonist (Ki=4.5 nM). JNJ-7777120 effectively blocks histamine-induced migration of mouse tracheal mast cells from connective tissue to epithelial cells. JNJ-7777120 also significantly blocks neutrophil infiltration in a mouse Zymosan-induced peritonitis model. JNJ-7777120 has a good potential to study antipruritic and anti-inflammatory[1][2]. |
| IC50& Target | |
体外研究
(In Vitro) | JNJ-7777120 (0, 10, 100, 1000 nM; ~6 h) shows functional antagonism of the human and mouse histamine H4 receptors in SK-N-MC cells[1].
JNJ-7777120 (10 μM; 10 min) blocks histamine-induced chemotaxis and calcium influx in mouse bone marrow-derived mast cells[1].
JNJ7777120 (30-100 μM; 30 min) inhibits dose-dependently the production of thymus and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 from antigen-stimulated BMMC[2].
Cell Viability Assay[1] | Cell Line: | SK-N-MC cells (expressing the human or mouse histamine H4 receptor) | | Concentration: | 0, 10, 100, 1000 nM | | Incubation Time: | ~6 h | | Result: | Exhibited antagonistic effect on human and mouse histamine H4 receptors. |
Immunofluorescence[1] | Cell Line: | Mouse mast cells | | Concentration: | 10 μM | | Incubation Time: | 10 min | | Result: | Exhibited a very potent antagonistic effect on the H4 receptor in primary cells. |
Cell Viability Assay[1] | Cell Line: | BMMC | | Concentration: | 30-100 μM | | Incubation Time: | 30 min | | Result: | Significantly inhibited the production of TARC (thymus and activation-regulated chemokine) and MDC (macrophage-derived chemokine). |
|
体内研究
(In Vivo) | JNJ-7777120 shows equipotent against the human, mouse, and rat receptors and exhibits at least 1000-fold selectivity over H1, H2, or H3receptors[1].
JNJ-7777120 has an oral bioavailability of ~30% in rats and 100% in dogs, with a half-life of ~3 h in both species[1].
JNJ-7777120 (20 mg/kg; s.c.; single daily for 2 days) blocks the histamine-induced migration of tracheal mast cells from the connective tissue toward the epithelium in mice[1].
JNJ-7777120 (10 mg/kg; s.c.; single) significantly blocks neutrophil infiltration in a mouse zymosan-induced peritonitis model[1].
| Animal Model: | BALB/c mice[1]. | | Dosage: | 20 mg/kg | | Administration: | Subcutaneous injection; single daily for 2 days | | Result: | Blocked histamine induced an increase in the number of mast cells per tracheal section and a significant migration of mast cells towards the tracheal epithelium. |
| Animal Model: | Male outbred Swiss albino mice (zymosan-induced peritonitis model)[1]. | | Dosage: | 10 mg/kg | | Administration: | Subcutaneous injection; single | | Result: | Led to a statistically significant reduction of neutrophil infiltration. |
|
| 分子量 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
|
| 溶解性数据 | In Vitro: DMSO : ≥ 50 mg/mL(180.02 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 3.6004 mL | 18.0018 mL | 36.0036 mL | | 5 mM | 0.7201 mL | 3.6004 mL | 7.2007 mL | | 10 mM | 0.3600 mL | 1.8002 mL | 3.6004 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (9.00 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (9.00 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (9.00 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (9.00 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (9.00 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (9.00 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
|
