ホーム>>Signaling Pathways>> MAPK Signaling>> JNK>>BI 78D3

BI 78D3 (Synonyms: JNK Inhibitor X, c-Jun N-terminal Kinase Inhibitor X)

カタログ番号GC12904

BI 78D3 は、JNK の基質競合阻害剤として機能し、JNK キナーゼ活性を阻害します (IC50=280 nM)。

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

BI 78D3 化学構造

Cas No.: 883065-90-5

サイズ 価格 在庫数 個数
5mg
$68.00
在庫あり
25mg
$245.00
在庫あり
50mg
$479.00
在庫あり

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

顧客レビュー

カスタマーレビューに基づきます。

  • 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:

The cell based kinase assays for c-Jun and ATF2 phosphorylation carry out by using the LanthaScreen c-Jun (1-79) HeLa and LanthaScreen ATF2 (19-106) A549 cell lines which stably express GFP-c-Jun 1-79 and GFP-ATF2 19-106, respectively. Phosphorylation is determined by measuring the time resolved FRET (TR-FRET) between a terbium labeled phospho-specific antibody and the GFP-fusion protein. The cells are plated in white tissue culture treated 384 well plates at a density of 10,000 cell per well in 32 μl assay medium (supplemented with 1% charcoal/dextran-treated FBS, 100 U/mL Penicillin and 100 μg/mL Streptomycin, 0.1 mM nonessential amino acids, 1 mM sodium pyruvate, 25 mM Hepes, pH 7.3, and lacking phenol red). After overnight incubation, cells are pretreated for 60 min with BI-78D3 (0.001, 0.01, 0.1, 1, 10, and 100 μM) followed by 30 min of stimulation with 2 ng/mL of TNF-α that stimulates both JNK and p38. The medium is then removed by aspiration and the cells are lysed by adding 20 μL of lysis buffer (20 mM Tris•HCl, pH 7.6, 5 mM EDTA, 1% Nonidet P-40 substitute, 5 mM NaF, 150 mM NaCl, and 1:100 protease and phosphatase inhibitor mix, SIGMA P8340 and P2850, respectively). The lysis buffer includs 2 nM of the terbium-labeled anti-pc-Jun (pSer73) or anti-pATF2 (pThr71) detection antibodies. After allowing the assay to equilibrate for 1 h at room temperature, TR-FRET emission ratios are determined on a BMG Pherastar fluorescence plate reader (excitation at 340 nm, emission 520 nm and 490 nm; 100 μs lag time, 200 μs integration time, emission ratio=Em520/Em 490)[1].

Cell experiment:

Mice[1]ConA and BI-78D3 is injected i.v. at 10 mg/kg into 6 to 8 weeks old male BL/6 mice. For partial hepatectomy, mice are anesthetized with isofluorane and subjected to midventral laparotomy followed by removal of the left lateral and median lobes. Animals are killed, blood is collected by cardiac puncture, and livers are surgically removed. Serum is separated and analyzed for alanine-aminotranferase levels[1].Eleven-week-old male BKS.Cg-+Leprdb/+Leprdb/OlaHsd db/db mice are randomized based on blood glucose levels acclimated three days before drug dosing. Blood glucose is read by using a hand-held glucose meter (Mice are fasted 6 h before i.p. (i.p.) administration of 25 mg/kg BI-78D3. Thirty minutes after test article administration, Bovine Insulin (I-0516 at 0.75 mg/kg) is administered via i.p. injection. Blood samples are taken at designated time points and blood glucose levels are measured as described. Food is returned three hours after test article administration[1].

References:

[1]. Stebbins JL et al. Identification of a new JNK inhibitor targeting the JNK-JIP interaction site. Proc Natl Acad Sci U S A, 2008 Oct 28, 105(43):16809-13.

Background

BI-78D3 is a substrate competitive inhibitor of JNK inhibitor [2].

JNK is a member of the MAPK family. JNK is a stress-activated protein kinase that modulates pathways implicated in a variety of disease states. Non-motoric JNK functions may differ between cell types and organs. The JNK is involved in a1-adrenoceptor-mediated contraction of prostate smooth muscle. For non-malignant, epithelial human prostate cells, JNK activation not only has the function of pro-apoptotic and antiproliferative but also related with JNK-dependent survival.[1]

BI-78D3 is competitive with ATF2 for binding to JNK1 with an apparent Ki value of 200 nM. In addition, it has been reported that BI-78D3 does not inhibit the phosphorylation of a short peptide substrate lacking a D-domain. This confirms that BI-78D3 is substrate competitive.[2]

BI-78D3 inhibits both noradrenaline- and phenylephrine-induced contractions. Then it prevents α1-adrenoceptor-mediated contraction of prostate tissue. As an effective JNK inhibitor, BI-78D3 has the ability of abrogating ConA-induced liver damage and restoring insulin sensitivity. [1,2]

References:
[1] Strittmatter F1, Walther S, Gratzke C, etal. , Inhibition of adrenergic human prostate smooth muscle contraction by the inhibitors of c-Jun N-terminal kinase, SP600125 and BI-78D3. Br J Pharmacol. 2012 Jul;166(6):1926-35.
[2] Stebbins JL, De SK, Machleidt T,etal.  , Identification of a new JNK inhibitor targeting the JNK-JIP interaction site. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16809-13.

Chemical Properties

Cas No. 883065-90-5 SDF
同義語 JNK Inhibitor X, c-Jun N-terminal Kinase Inhibitor X
Chemical Name 4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-((5-nitrothiazol-2-yl)thio)-4H-1,2,4-triazol-3-ol
Canonical SMILES OC1=NN=C(SC2=NC=C(S2)N(=O)=O)N1C3=CC4=C(OCCO4)C=C3
Formula C13H9N5O5S2 M.Wt 379.37
溶解度 DMF: 33 mg/ml,DMSO: 33 mg/ml,DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml 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 2.6359 mL 13.1797 mL 26.3595 mL
5 mM 0.5272 mL 2.6359 mL 5.2719 mL
10 mM 0.2636 mL 1.318 mL 2.6359 mL
  • モルアリティ計算機

  • 希釈計算機

質量
=
濃度
x
容積
x
MW*
 
 
 
**ストックソリューションを準備する際には、常にバイアルラベルおよび MSDS/CoA(オンラインで利用可能)で掲載された製品のロット固有分子量を使用してください。

計算

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.

レビュー

Review for BI 78D3

Average Rating: 5 ★★★★★ (Based on Reviews and 19 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for BI 78D3

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.