JNK Inhibitor VIII

製品コードS7794 バッチS779401

印刷

化学情報

Synonyms

TCS JNK 6o

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₁₈H₂₀N₄O₄

分子量

356.38

CAS No.

894804-07-0

Solubility (25°C)*

体外

DMSO

71 mg/mL (199.22 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	3.55mg/ml
	5% DMSO 1 95% Corn oil	1.7mg/ml

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	JNK Inhibitor VIII (TCS JNK 6o) is an inhibitor of c-Jun N-terminal kinases with IC50 of 45 nM and 160 nM for JNK-1 and JNK-2, respectively. JNK Inhibitor VIII (TCS JNK 6o) inihibits JNK-1, JNK-2, and JNK-3 with Ki of 2 nM, 4 nM and 52 nM, respectively.
in vitro	TCS-JNK-6a binds competitively and reversibly to the ATP site. This compound demonstrates a remarkable selectivity profile. Additionally, it shows some inhibition of c-Jun phosphorylation in hepG2 cells. TCS-JNK-6o is a 2,5-dimethoxy analogue of TCS-JNK-6a with the dimethoxy substitution of the phenyl ring. TCS-JNK-6o shows further gains in potency.^[1]
in vivo	Pharmacokinetic profiles are determined for JNK Inhibitor VIII (TCS-JNK-6o) in Sprague-Dawley rats. JNK Inhibitor VIII (TCS-JNK-6o) showes a short half-life of roughly 1 h, with rapid clearance and barely measurable bioavailability. Microsomal incubation studies revealed that oxidative metabolism is very rapid with this compound.^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	Ser/Thr-kinase
キナーゼアッセイ	Ser/Thr-kinase assays are performed using a radioactive FlashPlate-based assay platform. In this format, biotinylated substrate peptide (2 μM), γ-[³³P]-ATP (5 μM, 2 mCi/μmol), inhibitors (3-10000 nM in 2% DMSO), and enzyme are incubated for 1 h in buffer containing 25 mM Hepes, pH 7.5, 1 mM DTT, 10 mM MgCl2, 100 μM Na3VO4, and 0.075 mg/mL Triton X-100, stopped with 80 μL of stop buffer containing 100 mM EDTA and 4 M NaCl, transferred to streptavidin-coated 384-well FlashPlates, which are then washed 3 times and read using a TopCount microplate reader.
細胞アッセイ	細胞株	hepG2 cells
	濃度	Serial concentrations
	反応時間	1 h
	実験の流れ	HepG2 human hepatoma cells (ATCC) are cultured in low glucose MEM supplemented with 1×NEAA, 1×sodium pyruvate, and 10% FBS. For P-c-Jun assays, cells are plated at 5×10⁴ cells/well in 500 μL of complete media on 24-well collagen-coated plates and incubated overnight. Serial compound dilutions are made in DMSO at 100×, and then 5 μL is added directly to the media on the cells to provide the final inhibitor concentrations. After 1 h, cells are stimulated with vehicle control or TNFR for 30 min and harvested in 70μL of lysis buffer (TBS (54 mM Tris-HCl, pH 7.6, 150 mM NaCl), 1% TritonX-100,0.5% Nonidet P-40, 0.25% sodium deoxycholate, 1 mM EDTA, 1 mM EGTA, 0.5 mM sodium fluoride, 1 mM pervanadate, 1 μM microcystin, 1 mM AEBSF, 1 tablet of complete EDTA Free-Mini inhibitor cocktail) and frozen at -80 °C prior to use in the P-c-Jun assay.
動物実験	動物モデル	Sprague-Dawley rat
	投薬量	5 mg/kg
	投与方法	IV, Oral gavage

参考

[1] Bruce G Szczepankiewicz, et al. J Med Chem. 2006 Jun 15;49(12):3563-80.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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Inhibition of JNK signaling in the Asian malaria vector Anopheles stephensi extends mosquito longevity and improves resistance to Plasmodium falciparum infection [ PLoS Pathog, 2018, 14(11):e1007418]	PubMed: 30496310
Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells [ PLoS One, 2015, 10(11):e0143685]	PubMed: 26606677

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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