(E/Z)-BIX02188

SKU: orb1300869

Description

BIX02188

Research Area

Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1094614-84-2
• MW: 412.48
• Purity: 97.39%
• Formula: C₂₅H₂₄N₄O₂
• SMILES: CN(C)Cc1cccc(NC(=C2C(=O)Nc3cc(ccc23)C(N)=O)c2ccccc2)c1
• Target: TGF-beta/Smad,Others,MEK,ERK
• Solubility: Ethanol:3 mg/mL (7.27 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:40 mg/mL (96.97 mM)

Bioactivity

• Target IC50:
  MEK5:4.3 nM|ERK5:810 nM
• In Vitro:
  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 Water2, 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.
• Cell Research:
  The 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.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

TGF-β/Smad, TGFβR1, TGFbeta, TGF-beta, TGFbeta/Smad, TGFβ, TGF-b/Smad, TGFb, Smad, BIX 02188, BIX02188, BIX-02188, 334949-59-6, MEK1, MEK5, MEK2, ERK5

Compound Identifiers

PubChem CID

135398492