Inicio>>Signaling Pathways>> JAK/STAT Signaling>> JAK>>PF-03394197(Oclacitinib)

PF-03394197(Oclacitinib) (Synonyms: PF-03394197)

Catalog No.GC14938

Novel Janus kinase inhibitor

Products are for research use only. Not for human use. We do not sell to patients.

PF-03394197(Oclacitinib) Chemical Structure

Cas No.: 1208319-26-9

Tamaño Precio Disponibilidad Cantidad
5mg
96,00 $
Disponible
10mg
184,00 $
Disponible
50mg
372,00 $
Disponible

Tel:(909) 407-4943 Email: sales@glpbio.com

Reseñas de cliente

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

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.

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.
[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.

Background

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.

Chemical Properties

Cas No. 1208319-26-9 SDF
Sinónimos PF-03394197
Chemical Name 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
Formula C15H23N5O2S M.Wt 337.44
Solubility ≥ 33.7mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
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
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Reseñas

Review for PF-03394197(Oclacitinib)

Average Rating: 5 ★★★★★ (Based on Reviews and 40 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for PF-03394197(Oclacitinib)

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.