现货大促销,价格低至8折起,量大更优惠,详细咨询客服
全部分类
全部分类
  • Oclacitinib maleate (PF-03394197 maleate)
Oclacitinib maleate (PF-03394197 maleate)的可视化放大

Oclacitinib maleate (PF-03394197 maleate)

A JAK family kinase inhibitor

原价
¥1075-8450
价格
860-6760
Oclacitinib maleate (PF-03394197 maleate)的二维码

所有产品仅用于科学研究,我们不为任何个人用途提供产品和服务

询价有惊喜,量大更优惠 点击这里给我发消息

  • 库存: 现货
可选包装 >>>
首页
  • 货号: ajce47596
  • CAS: 1640292-55-2
  • 别名: 奥拉替尼马来酸盐; PF-03394197 maleate
  • 分子式: C19H27N5O6S
  • 分子量: 453.51
  • 纯度: >98%
  • 溶解度: DMSO : ≥ 100 mg/mL (220.50 mM)
  • 储存: Store at -20°C
  • 库存: 现货

Background

Oclacitinib is an inhibitor of the JAK family kinases JAK1, JAK2, JAK3, and TYK2 (IC50s = 10, 18, 99, and 84 nM, respectively).1 It is selective for JAK kinases over a panel of 38 additional kinases at 1 μM. Oclacitinib inhibits LPS-induced increases in IL-12 and TNF-α levels in murine bone marrow-derived dendritic cells (BMDCs) in a concentration-dependent manner.2 Topical administration of oclacitinib (0.1, 0.25, and 0.5%) reduces scratching behavior and ear edema, as well as decreases levels of IL-1β, IL-4, and IL-6 in ear skin, in a mouse model of allergic dermatitis induced by toluene-2,3-diisocyanate (TDI). Formulations containing oclacitinib have been used in the treatment of pruritus associated with allergic dermatitis and the control of atopic dermatitis in dogs.


1.Gonzales, A.J., Bowman, J.W., Fici, G.J., et al.Oclacitinib (APOQUEL?) is a novel Janus kinase inhibitor with activity against cytokines involved in allergyJ. Vet. Pharmacol. Ther.37(4)317-324(2014) 2.Fukuyama, T., Ehling, S., Cook, E., et al.Topically administered Janus-kinase inhibitors ofacitinib and olacitinib dsplay impressive antipruritic and anti-inflammatory responses in a model of allergic dermatitisJ. Pharmacol. Exp. Ther.354(3)394-405(2015)

Protocol

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.

参考文献:

[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.
[2]. Fukuyama T, et al. Topically Administered Janus-Kinase Inhibitors Tofacitinib and Oclacitinib Display Impressive Antipruritic and Anti-Inflammatory Responses in a Model of Allergic Dermatitis. J Pharmacol Exp Ther. 2015 Sep;354(3):394-405.
[3]. Cosgrove SB, et al. 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.

动态评分

0.0

没有评分数据
没有评价数据
一键回到顶部
展开 收缩
安捷凯在线客服