PF-03394197(Oclacitinib)
(Synonyms: 奥拉替尼) 目录号 : GC14938
A JAK family kinase inhibitor
Cas No.:1208319-26-9
Sample solution is provided at 25 µL, 10mM.
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Description:
IC50: 10 nM for JAK1
Janus kinase (JAK) enzymes are involved in cell signaling pathways activated by cytokines dysregulated in allergy. PF-03394197 (Oclacitinib) is a novel Janus kinase inhibitor.
In vitro: PF-03394197 inhibited JAK family members by 50% at concentrations ranging from 10 to 99 nM and did not inhibit a panel of 38 non-JAK kinases. PF-03394197 was most potent at inhibiting JAK1. PF-03394197 also inhibited the function of JAK1-dependent cytokines involved in allergy and inflammation as well as pruritus. PF-03394197 had minimal effects on cytokines which did not activate the JAK1 enzyme in cells [1].
In vivo: PF-03394197 administered orally at a dose of 0.4–0.6 mg/kg twice daily was safe and efficacious in controlling the pruritus associated with allergic dermatitis. PF-03394197 provided itch relief within 24 h that persisted through the treatment period, with over 70% of the treated dogs achieving a >50% reduction in pruritus by day 7 [2].
Clinical trial: PF-03394197 (Oclacitinib) (APOQUEL?) has recently been approved in the United States and European Union for the control or treatment of pruritus associated with allergic dermatitis and the control or treatment of AD in dogs [1].
Reference:
[1] Gonzales AJ, Bowman JW, Fici GJ, Zhang M, Mann DW, Mitton-Fry M. Oclacitinib (APOQUEL(?)) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy. J Vet Pharmacol Ther. 2014 Aug;37(4):317-24.
[2] Cosgrove SB, Wren JA, Cleaver DM, Martin DD, Walsh KF, Harfst JA, Follis SL, King VL, Boucher JF, Stegemann MR. Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis. Vet Dermatol. 2013 Oct;24(5):479-e114.
Kinase experiment: | Recombinant human active kinase domains for JAK1, JAK2, JAK3, and TYK2 are used in isolated enzyme assays using Caliper microfluidics technology to determine potency of Oclacitinib against the JAK family members. Sequence homology to the analogous sequences in the canine JAK enzymes are 98, 98, 100, and 90%, respectively. Invitrogen kinase panel testing is performed to determine potency of Oclacitinib toward 38 different non-JAK kinases using their SelectScreen Kinase Profiling Services. Oclacitinib is evaluated at a concentration of 1 μM[1]. |
Animal experiment: | Mice[2]BALB/cAnN (female, 6 weeks old) are used. The JAK inhibitors (Tofacitinib or Oclacitinib) are administered orally or topically 30 minutes before and 4 hours after toluene-2,4-diisocyanate (TDI) challenge because the absorption of Tofacitinib and Oclacitinib is rapid, with plasma concentrations for both Tofacitinib and Oclacitinib peaking at around 1 hour after oral or intravenous administration. Tofacitinib and Oclacitinib both have a short half-life of 2 and 4 hours after administration, respectively. Each drug is diluted in a 0.5% methylcellulose/0.25% Tween 20 solution for oral administration, and a 7:1 acetone:DMSO solution for topical application to concentrations described subsequently. For each drug, a vehicle-only control group and low- and high-dose groups are set. Oral doses are as follows: Tofacitinib, 10 and 30 mg/kg; and Oclacitinib, 30 and 45 mg/kg. Topically administered doses are 0.1, 0.25, and 0.5% for both chemicals. The oral doses of Tofacitinib and Oclacitinib used in this study are selected.Dogs[3]Dogs are randomized to one of two treatment groups (i.e. Oclacitinib or placebo) in a 1:1 ratio. Dogs in the Oclacitinib treatment group are given Oclacitinib maleate caplets orally at a dose of 0.4-0.6 mg/kg twice daily. The scored caplets are provided in three strengths containing 3.6, 5.4 and 16 mg of Oclacitinib. Dogs in the placebo treatment group are given the same number of caplets, identical in appearance to Oclacitinib maleate caplets and containing all of the same excipients except Oclacitinib maleate. |
References: [1]. Gonzales AJ, et al. Oclacitinib (APOQUEL) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy. J Vet Pharmacol Ther. 2014 Aug;37(4):317-24. | |
| Cas No. | 1208319-26-9 | SDF | |
| 别名 | 奥拉替尼 | ||
| 化学名 | N-methyl-1-((1r,4r)-4-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclohexyl)methanesulfonamide | ||
| Canonical SMILES | CNS(C[C@@]1([H])CC[C@@](N(C2=NC=NC3=C2C=CN3)C)([H])CC1)(=O)=O | ||
| 分子式 | C15H23N5O2S | 分子量 | 337.44 |
| 溶解度 | ≥ 33.7mg/mL in DMSO | 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 | 2.9635 mL | 14.8174 mL | 29.6349 mL |
| 5 mM | 0.5927 mL | 2.9635 mL | 5.927 mL |
| 10 mM | 0.2963 mL | 1.4817 mL | 2.9635 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
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet