CEP-33779 |
Catalog No.GC12083 |
A potent, orally available inhibitor of JAK2
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1257704-57-6
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | The kinase activity of baculovirus-expressed human JAK1, JAK2, or JAK3 is measured. Each 96-well Costar high binding plate is coated with 100 μL/well of 10 μg/mL neutravidin in TBS at 37 °C for 2 h, followed by 100 μL/well of 1 μg/mL 15-mer peptide substrate at 37 °C for 1 h. The kinase assay mixture (total volume=100 μL/well) consisting of 20 mM HEPES (pH 7.2), ATP (0.2 μM ATP for JAK1 and JAK2 and 0.1 μM ATP for JAK3), 1 mM MnCl2, 0.1% BSA, and CEP-33779 (diluted in DMSO, 2.5% DMSO final in assay) is added to the assay plate. Enzyme is added and the reaction is allowed to proceed for 20 min at room temperature. Detection of the phosphorylated product is performed by adding 100 μL/well of diluted Eu-N1 labeled PY100 antibody. Samples are incubated at RT for 1 h, followed by addition of 100 μL enhancement solution. Plates are agitated for 10 min, and the fluorescence of the resulting solution is measured. IC50 values are determined[1]. |
Animal experiment: | Mice: Nude mice bearing CWR22 xenografts are dosed orally with 55 mg/kg of CEP-33779 or a vehicle (PEG400). At 2, 6, and 24 h after dosing animals (3/group) are sacrificed, tumors are excised and plasma samples are prepared. Tumor extracts are prepared using Triton-based extraction buffer supplemented with inhibitors of proteases and phosphatases. Equal amounts of extracts are resolved on SDS-PAGE gels and STAT3 phosphorylation and expression are analyzed by Western blot using specific antibodies[1]. |
References: [1]. Dugan BJ, et al. A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779. J Med Chem. 2012 Jun 14;55(11):5243-54. |
CEP-33779, is a highly selective, orally active inhibitor of Janus kinase 2 (JAK2). When evaluate against the other members of the JAK family, CEP-33779 demonstrates varying degrees of selectivity from >40-fold versus JAK1 to >800-fold against TYK2. In a cellular system, CEP-33779 is shown to inhibit JAK2 in irf-bla TF-1 cells utilizing the GeneBLAzer reporter assay. It is also able to mitigate several immune parameters associated with SLE advancement, including the protection and treatment of mice with lupus nephritis. The ability of CEP-33779 to suppress growth of colorectal tumors by inhibiting the IL-6/JAK2/STAT3 signaling suggests a potential therapeutic utility of JAK2 inhibitors in multiple tumors types, particularly those with a strong inflammatory component.
Reference
[1].Kristine L Stump, Lily D Lu, Pawel Dobrzanski, Cynthia Serdikoff, Diane E Gingrich, Ben J Dugan, Thelma S Angeles, Mark S Albom, Mark A Ator, Bruce D Dorsey, Bruce A Ruggeri, Matthew M Seavey. A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease in two mouse models of rheumatoid arthritis. Arthritis Research & Therapy 2011, 13:R68.
[2].Lily D. Lu, Kristine L. Stump, Nate H. Wallace, Pawel Dobrzanski, Cynthia Serdikoff, Diane E. Gingrich, Benjamin J. Dugan, Thelma S. Angeles, Mark S. Albom, Jennifer L. Mason, Mark A. Ator, Bruce D. Dorsey, Bruce A. Ruggeri, Matthew M. Seavey. Depletion of Autoreactive Plasma Cells and Treatment of Lupus Nephritis in Mice Using CEP-33779, a Novel, Orally Active, Selective Inhibitor of JAK2. The Journal of Immunology October 1, 2011 vol. 187 no. 7 3840-3853.
[3].Matthew M. Seavey, Lily D. Lu, Kristine L. Stump, Nate H. Wallace, William Hockeimer, Teresa M. O'Kane, Bruce A. Ruggeri, Pawel Dobrzanski. Therapeutic Efficacy of CEP-33779, a Novel Selective JAK2 Inhibitor, in a Mouse Model of Colitis-Induced Colorectal Cancer. Mol Cancer Ther April 2012 11; 984.
Cas No. | 1257704-57-6 | SDF | |
Chemical Name | N-[3-(4-methylpiperazin-1-yl)phenyl]-8-(4-methylsulfonylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine | ||
Canonical SMILES | CN1CCN(CC1)C2=CC(=CC=C2)NC3=NN4C=CC=C(C4=N3)C5=CC=C(C=C5)S(=O)(=O)C | ||
Formula | C24H26N6O2S | M.Wt | 462.57 |
Solubility | ≥ 23.15 mg/mL in DMSO with gentle warming | 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. |
Prepare stock solution | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.1618 mL | 10.8092 mL | 21.6183 mL |
5 mM | 0.4324 mL | 2.1618 mL | 4.3237 mL |
10 mM | 0.2162 mL | 1.0809 mL | 2.1618 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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.)
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.
Average Rating: 5
(Based on Reviews and 30 reference(s) in Google Scholar.)GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *