CR4056
目录号 : GC31094
CR4056是一个选择性的人重组MAO-A抑制剂，其IC50值为202.7nM。CR4056也是咪唑啉-2受体(I2R)的配体，其IC50值为596nM。
Cas No.:1004997-71-0
Sample solution is provided at 25 µL, 10mM.
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CR4056 is a selective inhibitor of human recombinant MAO-A with an IC50 of 202.7 nM. CR4056 is also a ligand of imidazoline-2 receptor (I2R) with an IC50 of 596 nM.
CR4056 is an imidazoline-2 receptor (I2R) ligand with an IC50 of 596±76 nM. CR4056 is also an inhibitor of both human recombinant MAO-A and MAO-B with IC50s of 202.7±10.3 and >10000, respectively[1]. The co-treatment of bortezomib (BTZ) with CR4056 at all the concentrations used (range 3 to 30 μM) does not induce any significant difference in cell survival compare with BTZ-treated cells, either in H929 or in RPMI 8226 myeloma cells[2].
Two hours after a single oral dose of 20 mg/kg CR4056, endogenous norepinephrine (NE) levels increase by 68.2%±14.1% (P<0.05 versus vehicle) in the parieto-occipital cortex. Sub-chronic (four days) oral treatment with 20 mg/kg CR4056 once daily, significantly increases NE levels both in the cerebral cortex (63.1%±4.2%; P<0.05 versus vehicle) and in the lumbar spinal cord (51.3%±6.7%; P<0.05 versus vehicle). CR4056 dose-dependently reduces mechanical hyperalgesia (effective dose [ED50]=5.8 mg/kg) (P<0.001). CR4056 (10 mg/kg) and piroxicam (10 mg/kg) significantly reverse the decrease in withdrawal threshold caused by capsaicin (P<0.001 versus vehicle). The highest tested dose of CR4056 (30 mg/kg) completely reverses the effect of capsaicin, increasing paw withdrawal threshold (PWT) to 239±12 g (P<0.001 versus vehicle) after 1 hour. CR4056 dose-dependently decreases streptozotocin (STZ)-induced diabetic pain in rats (F[4, 35]=31.27, P<0.001). CR4056 significantly increases the mechanical withdrawal thresholds of both ipsilateral (F[4, 30]=19.97, P<0.001) and contralateral (F[4, 30]=31.58, P<0.001) hind paws compare with vehicle control[1].
[1]. Ferrari F, et al. Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain. J Pain Res. 2011;4:111-25. [2]. Meregalli C, et al. CR4056, a new analgesic I2 ligand, is highly effective against bortezomib-induced painful neuropathy in rats. J Pain Res. 2012;5:151-67.
Kinase experiment: | Binding assays on monoamine oxidases in rat cerebral cortical membranes are conducted. In summary, for the MAO-A binding assay, tritiated N-(2-aminoethyl)-5-(m-fluorophenyl)-4-thiazole carboxamide HCl ([3H]Ro 41-1049, 10 nM) is incubated in the absence or presence of CR4056 for 60 minutes at 37°C and non specific binding is determined in the presence of 1 μM clorgyline. For the MAO-B binding assay, incubation of [3H]Ro 19-6327(tritiated lazabemide) (15 nM) is carried out for 90 minutes at 22°C and non specific binding is determined in the presence of 10 μM (R)-deprenyl [1]. |
Cell experiment: | To rule out any interference of CR4056 with bortezomib (BTZ)-induced cytotoxicity, non-small cell lung cancer and MM cell lines are simultaneously treated for 72 hours with BTZ and CR4056. Cells are exposed to the IC50 of BTZ, estimated in the cytotoxicity study, with or without three concentrations of CR4056 (3, 10, and 30 μM). The incubations with CR4056 alone (3, 10, and 30 μM) and with the highest dose of vehicle (DMSO) are also performed. Growth inhibition is assessed by MTT assay. In these experiments, the CR4056 is tested in vitro in a range of concentrations spanning from pharmacological to toxicological levels[2]. |
Animal experiment: | Rats: Rats are fasted overnight before drug administration. A first measurement of pain threshold is undertaken before capsaicin injection. Capsaicin is administered at time t=0 by the intraplantar route in the right hind paw (10 μL of a 1 mg/mL Tween 80/saline solution). Sixty minutes later, animals are dosed by the oral route with CR4056 (3 to 30 mg/kg) or its vehicle in a volume of 5 mL/kg. A sham control group is always present for comparison. In mechanistic studies, antagonists are administered 30 minutes after capsaicin and 15 minutes before CR4056 administration[1]. |
References: [1]. Ferrari F, et al. Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain. J Pain Res. 2011;4:111-25. | |
| Cas No. | 1004997-71-0 | SDF | |
| Canonical SMILES | C1(C2=CC=CC=C2)=NC=C3C=C(N4C=CN=C4)C=CC3=N1 | ||
| 分子式 | C17H12N4 | 分子量 | 272.3 |
| 溶解度 | DMSO : 30 mg/mL (110.17 mM) | 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 | 3.6724 mL | 18.3621 mL | 36.7242 mL |
| 5 mM | 0.7345 mL | 3.6724 mL | 7.3448 mL |
| 10 mM | 0.3672 mL | 1.8362 mL | 3.6724 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。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet