RVT-501
(Synonyms: RVT-501; E6005) 目录号 : GC19314
An inhibitor of PDE4
Cas No.:947620-48-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | PDE isoenzyme activities are quantified by measuring the formation of [3H]5′-AMP or [[3H]5′-GMP from [[3H]cAMP or [[3H]cGMP using an enzyme isolated from bovine brain (for PDE1), differentiated U-937 cells (for PDE2), human platelets (for PDE3 and PDE5), and U-937 cells (for PDE4). The test compounds (RVT-501), reference compounds, or vehicle (water) is added to a reaction buffer. The reaction is initialized by addition of the enzyme, and the mixture is incubated for 60 minutes at 22°C. After incubation, the reaction is stopped by heating the plate to 60°C for 3 minutes, after which time scintillation proximity assay beads are added. After 20 minutes of shaking at 22°C, the amount of [[3H]5′-AMP or [[3H]5′-GMP is quantified with a scintillation counters[1]. |
Animal experiment: | Mice: Lotamilast is applied to the hair-clipped rostral back. Observation of hind-paw scratching and electrophysiological recording of the cutaneous nerve branch are conducted. The effects of topical application of E6005 are evaluated 1 h after application, because topical application of the vehicle elicited hind-paw scratching for 40 min. The cutaneous concentration of cAMP is measured by enzyme immunoassay[2]. |
References: [1]. Ishii N, et al. Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12. | |
RVT-501 (E6005) is a selective phosphodiesterase 4 (PDE4) inhibitor with an IC50 of 2.8 nM.
RVT-501 potently and selectively inhibits human PDE4 activity with an IC50 of 2.8 nM and suppresses the production of various cytokines from human lymphocytes and monocytes with IC50 values ranging from 0.49 to 3.1 nM[1].
RVT-501 is currently in phase 2 development for patients with mild-to-moderate atopic dermatitis. In mice models, the topical application of RVT-501 produces an immediate antipruritic effect as well as an anti-inflammatory effect with reduced expression of cytokines/adhesion molecules. On the basis of these observed effects, topical RVT-501 ameliorates the appearance of atopic dermatitis-like skin lesions in two types of AD models, hapten- and mite-elicited models, exhibiting inhibitory effects comparable to that of tacrolimus[1]. A single topical application of RVT-501 significantly inhibits spontaneous scratching during 1-2 h after application in mice with chronic dermatitis; the inhibition is partial and similar between 0.01% and 0.03%. Topical application of 0.03% RVT-501 to the rostral back significantly inhibits the increased activity of the cutaneous nerve in mice with chronic dermatitis. The cutaneous concentration of cAMP is significantly decreased in mice with chronic dermatitis, and this decrease is reversed by topical RVT-501 application[2].
References:
[1]. Ishii N, et al. Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12.
[2]. Andoh T, et al. Topical E6005, a novel phosphodiesterase 4 inhibitor, attenuates spontaneous itch-related responses in mice with chronic atopy-like dermatitis. Exp Dermatol. 2014 May;23(5):359-61.
| Cas No. | 947620-48-6 | SDF | |
| 别名 | RVT-501; E6005 | ||
| Canonical SMILES | O=C(C1=CC=C(C(OC)=O)C=C1)NC2=CC=CC(C3=C4C(C=C(OC)C(OC)=C4)=NC(NC)=N3)=C2 | ||
| 分子式 | C26H24N4O5 | 分子量 | 472.49 |
| 溶解度 | DMSO : ≥ 100 mg/mL (211.64 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 | 2.1164 mL | 10.5822 mL | 21.1645 mL |
| 5 mM | 0.4233 mL | 2.1164 mL | 4.2329 mL |
| 10 mM | 0.2116 mL | 1.0582 mL | 2.1164 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。