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    BIX 02188
    BIX 02188

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0457
    CAS #: 334949-59-6Purity ≥98%

    Description: BIX02188 (BIX-02188), an indolinone analog, is a novel, highly potent and selective MEK5 inhibitor with the potential to relieve neuropathic pain. It inhibits MEK5 with IC50 of 4.3 nM, and also shows inhibition against ERK5 with an IC50 of 810 nM, but has no effects on closely related kinases MEK1, MEK2, ERK2, and JNK2. Selective inhibiting of p-ERK5 expression in CSF-CN by BIX02188 could significantly relieve CCI-induced mechanical allodynia and thermal hypersensitivity, accompanying with the decreased phosphorylation of cAMP response-element binding protein (CREB) in CSF-CN.

    References: Biochem Biophys Res Commun. 2008;377:120-5; Biochem Biophys Res Commun. 2008;370:159-63.

    Related CAS: 1094614-84-2; 334949-59-6 

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    • YALE
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    • 香港大学
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    Molecular Weight (MW)412.48
    FormulaC25H24N4O2
    CAS No.334949-59-6; 
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 43 mg/mL (104.2 mM)
    Water: <1 mg/mL
    Ethanol: 3 mg/mL (7.3 mM)
    Solubility (In vivo)30% PEG400+0.5% Tween80+5% propylene glycol: 30mg/mL
    Synonyms

    BIX-02188; BIX 02188; BIX02188

    Chemical Name: (Z)-3-(((3-((dimethylamino)methyl)phenyl)amino)(phenyl)methylene)-2-oxoindoline-6-carboxamide

    InChi Key: FSZPIAXLCCQFCM-FCQUAONHSA-N

    InChi Code: InChI=1S/C25H24N4O2/c1-29(2)15-16-7-6-10-19(13-16)27-23(17-8-4-3-5-9-17)22-20-12-11-18(24(26)30)14-21(20)28-25(22)31/h3-14,27H,15H2,1-2H3,(H2,26,30)(H,28,31)/b23-22-

    SMILES Code: CN(CC1=CC(N/C(C2=CC=CC=C2)=C3C(NC4=C\3C=CC(C(N)=O)=C4)=O)=CC=C1)C 


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    In Vitro

    In vitro activity: BIX02188 significantly blocks MEK5 catalytic activity with IC50 of 4.3 nM and inhibits ERK5 catalytic activity with IC50 of 0.83 μM. It shows no activity against closely related kinases MEK1, MEK2, ERK1, p38α, JNK2, TGFβR1, EGFR, and STK16 with IC50 values of 1.8 μM for TGFβR1, 3.9 μM for p38α, and >6.3 μM for other kinases. Pretreatment with BIX02188 inhibits sorbitol-induced phosphorylation of ERK5 in HeLa cells in a dose dependent manner and displays no inhibitory activity against the phosphorylation of ERK1/2, p38, and JNK1/2 MAPKs. BIX02188 treatment alone for 24 hours in HeLa or HEK293 cells does not show any cytotoxic effect. BIX02188 inhibits transcriptional activation of MEF2C through the MEK5/ERK5 signaling cascade in active MEK5/ERK5/MEF2C-driven luciferase expression system in HeLa and HEK293 cells with IC50 values of 1.15 μM and 0.82 μM, respectively. BIX02188 also inhibits phosphorylation of BMK1 in bovine lung microvascular endothelial cells (BLMECs) which are stimulated with 300 μM H2O2, in a dose-dependent manner, with IC50 of 0.8 μM, specifically by blocking the MEK5 signal pathway. BIX02188 completely reverses the inhibitory effect on TNF-mediation; JNK activation had a similar effect on BMK1 inhibition, suggesting that it inhibits TNF signaling through activation of the MEK5-BMK1 signaling pathway.


    Kinase Assay: MEK5 protein isolated from a baculovirus expression system is used to measure kinase activity utilizing PKLight ATP Detection Reagent. The assay is performed using 15 nM GST-MEK5 and 0.75 μM ATP in assay buffer consisting of 25 mM Hepes, pH 7.5, 10 mM MgCl2, 50 mM KCl, 0.2% BSA, 0.01% CHAPS, 100 μM Na3VO4, 0.5 mM DTT and 1% DMSO in the presence of varying concentrations of BIX02188. The kinase reaction mixture is incubated for 90 minutes at room temperature followed by addition of 10 μL of an ATP detection reagent for 15 minutes. The relative light unit (RLU) signal is measured and the RLU signals are converted to percent of control (POC) values for the determination of IC50 value.


    Cell Assay: The HeLa cells are serum starved for 20 hours prior to stimulation with sorbitol at a final concentration of 0.4 M for 20 minutes at 37 °C. BIX02188 is added 1.5 hours prior to the addition of sorbitol. The cells are harvested and lysed in 50 μL RIPA buffer containing Halt protease and phosphate inhibitors at 4 °C for 5-10 minutes. The lysates are centrifuged for 10 minutes at 14,000 rpm and 50 μL lysate is added to 50 μl 2× sample buffer and boiled for 4 minutes at 95 °C. A 20 µl sample is run on SDS–PAGE 10% Tris-glycine gels and transferred to nitrocellulose. Western blotting is done with appropriate antibodies.

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    References

    Biochem Biophys Res Commun. 2008 Dec 5;377(1):120-5; Biochem Biophys Res Commun. 2008 May 23;370(1):159-63.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    BIX 02188

    BIX02188 reverses flow inhibition of TNF-induced signaling. Fluid shear stress inhibits TNF-mediated JNK activation via MEK5-BMK1 in endothelial cells. Biochem Biophys Res Commun. 2008 May 23;370(1):159-63.


    BIX 02188

    Regulation of podocyte apoptosis via Erk5.  2014 Apr 21;5:71. 

    BIX 02188

    Regulation of podocyte proliferation via Erk5.


    BIX 02188

    Regulation of podocyte barrier function via Erk5.  2014 Apr 21;5:71. 

    BIX 02188

    Regulation of podocyte motility via Erk5.


    BIX 02188

    Erk5 expression, activation, and subcellular localisation in podocytes via TGFβ1.  2014 Apr 21;5:71. 


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