INCB38579
目录号 : GC65937
INCB38579 是一种具有口服活性、高度脑穿透和选择性的组胺 H4 受体 (HH4R) 拮抗剂 (hH4R IC50=4.8 nM, mH4R IC50=42 nM, rH4R IC50=32 nM)。INCB38579 具有抗炎和抗瘙痒的活性。
Cas No.:1246207-65-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
INCB38579 is an orally active, highly brain penetrable, and selective histamine H4 receptor (HH4R) antagonist (hH4R IC50=4.8 nM, mH4R IC50=42 nM, rH4R IC50=32 nM). INCB38579 shows anti-inflammatory pain and anti-pruritic activities[1].
INCB38579 (0.1 nM-10 μM; 1.5 h) inhibits histamine binding to the recombinant human and rodent histamine H4 receptors[1].
INCB38579 (0.1 nM-10 μM; 20 min) blocks histamine-induced migration of dendritic cells differentiated from human monocytes and mouse bone marrow cells[1].
NCB38579 (0-30 nM; 1.5 h) inhibits histamine-induced cell shape change and migration of purified human eosinophils dose-dependently[1].
Cell Viability Assay[1]
| Cell Line: | HEK293 cells |
| Concentration: | 0.1 nM-10 μM |
| Incubation Time: | 1.5 hours |
| Result: | Showed the IC50 values of 4.8, 42 and 21 nM for the human, mouse and rat histamine H4 receptors, respectively. |
Cell Viability Assay[1]
| Cell Line: | Human monocytes, mouse bone marrow cells, and human eosinophils |
| Concentration: | 0.1 nM-10 μM |
| Incubation Time: | 20 min |
| Result: | Showed IC50s of 13.2 and 77 nM for human monocytes and mouse bone marrow cells，respectively. Showed IC50 values of approximately 20-30 nM for purified human eosinophils. |
Cell Viability Assay[1]
| Cell Line: | HEK293 cells |
| Concentration: | 0-30 nM |
| Incubation Time: | 1.5 hours |
| Result: | Showed the IC50 values of 4.8, 42 and 21 nM for the human, mouse and rat histamine H4 receptors, respectively. |
INCB38579 (oral gavage; 100 mg/kg; once) inhibits histamine-mediated pruritus in mice[1].
INCB38579 (oral gavage; 100 mg/kg; once) shows antinociceptive functions in this acute model of inflammatory pain[1].
INCB38579 (oral gavage; 3, 10, 30, and 100 mg/kg; once) inhibits formalin-induced pain in rats and mice[1].
| Animal Model: | Female CD-1 mice histamine-induced pruritus[1] |
| Dosage: | 100 mg/kg |
| Administration: | Oral gavage; 100 mg/kg; once |
| Result: | Reduced the number of scratching bouts significantly (P<0.05). |
| Animal Model: | Sprague-Dawley rats injected with carrageenan[1] |
| Dosage: | 100 mg/kg |
| Administration: | Oral gavage; 100 mg/kg; once |
| Result: | Increased the paw withdrawal threshold from a baseline of 61 g to approximately 100 g, achieving approximately 60% in maximal possible effect. |
| Animal Model: | Male Sprague-Dawley rats and male ICR mice injected with formalin into the hind paws[1] |
| Dosage: | 3, 10, 30, and 100 mg/kg |
| Administration: | Oral gavage; 3, 10, 30, and 100 mg/kg; once |
| Result: | Showed a significant dose-dependent analgesic effect from 10 to 100 mg/kg in the phase 1 response and 30 to 100 mg/kg in the phase 2 response in the mouse formalin test. Observed a dose-dependent and statistically significant effect in the phase 1 response, ranging from10 to 100 mg/kg, in the rat formalin test. |
| Cas No. | 1246207-65-7 | SDF | Download SDF |
| 分子式 | C25H34N6O | 分子量 | 434.58 |
| 溶解度 | DMSO : 230 mg/mL (529.25 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3011 mL | 11.5054 mL | 23.0107 mL |
| 5 mM | 0.4602 mL | 2.3011 mL | 4.6021 mL |
| 10 mM | 0.2301 mL | 1.1505 mL | 2.3011 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
INCB38579, a novel and potent histamine H₄ receptor small molecule antagonist with anti-inflammatory pain and anti-pruritic functions
Eur J Pharmacol 2012 Jan 30;675(1-3):47-56.PMID:22155710DOI:10.1016/j.ejphar.2011.11.027
The histamine H₄ receptor mediates several histamine-induced cellular functions of leukocytes, including cell migration and cytokine production. Recent studies suggest that histamine signaling through the histamine H₄ receptor can also have anti-pruritic and anti-nociceptive functions. 1-(7-(2-amino-6-(4-methylpiperazin-1-yl) pyrimidin-4-yl)-3, 4-dihdroisoquinolin-2(1H)-yl)-2-cyclopentylethanone (INCB38579) is a novel small molecule antagonist of the human and rodent histamine H₄ receptors with at least 80-fold selectivity over the human histamine H₁, H₂ and H₃ receptors, and has good pharmacokinetic properties in rats and mice. The compound is potent in inhibiting histamine binding to and signaling through the recombinant human, mouse and rat histamine H₄ receptors and blocks the histamine-induced migration of human and mouse dendritic cells, as well as the cell shape change and migration of human eosinophils. INCB38579 and histamine may have separate but overlapping binding sites on the human histamine H₄ receptor. This novel inhibitor is efficacious when evaluated in two previously established in vivo models for histamine H₄ receptor activity (histamine-induced itch in mice and carrageenan-induced acute inflammatory pain in rats). When examined in formalin-induced pain models, INCB38579 significantly reduces the sustained inflammatory pain experienced by rats and mice. A good correlation between the protein binding adjusted potency from in vitro studies and its analgesic effect in vivo was observed. These results suggest that INCB38579 can serve as a useful tool for pharmacologic characterization of the histamine H₄ receptor and further support the hypothesis that targeting the histamine H₄ receptor may provide new therapeutic agents for various chronic inflammatory diseases, including inflammatory pain.