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）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	3.550mg/ml (9.96mM)
	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.700mg/ml (4.77mM)

* <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)は、c-Jun N末端キナーゼの阻害剤で、JNK-1とJNK-2に対するIC50値はそれぞれ45 nMと160 nMです。JNK Inhibitor VIII (TCS JNK 6o)は、JNK-1、JNK-2、JNK-3をそれぞれ2 nM、4 nM、52 nMのKiで阻害します。
in vitro	JNK Inhibitor VIII (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 this chemical with the dimethoxy substitution of the phenyl ring. This compound shows further gains in potency.
in vivo	Pharmacokinetic profiles are determined for JNK Inhibitor VIII (TCS-JNK-6o) in Sprague-Dawley rats. This compound shows 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.

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), this compound (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

https://pubmed.ncbi.nlm.nih.gov/16759099/

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：

The ribotoxic stress response drives UV-mediated cell death [ Cell, 2024, 187(14):3652-3670.e40]	PubMed: 38843833
Blocking GSDME-mediated pyroptosis in renal tubular epithelial cells alleviates disease activity in lupus mice [ Cell Death Discov, 2022, 8(1):113]	PubMed: 35279675
Dabrafenib Promotes Schwann Cell Differentiation by Inhibition of the MEK-ERK Pathway [ Molecules, 2021, 26(8)2141]	PubMed: 33917810
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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