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CEP-33779

カタログ番号GC12083

JAK2の強力な経口阻害剤

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CEP-33779 化学構造

Cas No.: 1257704-57-6

サイズ 価格 在庫数 個数
10mM (in 1mL DMSO)
$185.00
在庫あり
5mg
$128.00
在庫あり
10mg
$181.00
在庫あり
50mg
$564.00
在庫あり
100mg
$824.00
在庫あり

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

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.
[2]. Seavey MM, et al. Therapeutic efficacy of CEP-33779, a novel selective JAK2 inhibitor, in a mouse model of colitis-induced colorectal cancer. Mol Cancer Ther. 2012 Apr;11(4):984-93.
[3]. Tang SJ, et al. CEP-33779 antagonizes ATP-binding cassette subfamily B member 1 mediated multidrug resistance by inhibiting its transport function. Biochem Pharmacol. 2014 Sep 15;91(2):144-56.

Background

CEP-33779は、Janusキナーゼ2(JAK2)の高度に選択的で経口的に有効な阻害剤です。 JAKファミリーの他のメンバーと比較して、CEP-33779はJAK1に対して40倍以上からTYK2に対して800倍以上まで異なる程度の選択性を示します。細胞系では、GeneBLAzerレポーターアッセイを利用したirf-bla TF-1細胞内でCEP-33779がJAK2を阻害することが示されています。また、ループス腎炎を持つマウスの保護や治療を含むSLE進行に関連するいくつかの免疫パラメーターを和らげることも可能です。IL-6 / JAK2 / STAT3シグナリングを阻害することで大腸癌の成長を抑制するCEP-33779の能力は、強い炎症性成分がある多数種類の腫瘍タイプでJAK2阻害剤の潜在的な治療効果を示唆しています。

参考文献

[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 およびMatthew M Seavey。Janus kinase 2の高度に選択的で経口的に有効な阻害剤CEP-33779はリウマチ性関節炎の2つのマウスモデルで疾患を消失させる。Arthritis Research & Therapy 2011年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,Mattew M.Seavey。JAK2の新規で経口的に有効な選択的阻害剤CEP-33779を用いた自己反応性プラズマ細胞の減少とループス腎炎治療法。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,Wiliam Hockeimer,Teresa M.O'Kane,Bruce A.Ruggeri,Pawel Dobrzanski。CEP-33779、新規選択的JAK2阻害剤のマウスモデルにおける治療効果:大腸炎誘発性大腸がん。Mol Cancer Ther April 2012 11;984.

Chemical Properties

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
溶解度 ≥ 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.

Complete Stock Solution Preparation Table

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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
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