BIX02188

SKU: orb1988758

Description

BIX02188 is a potent and selective MEK5 inhibitor. It blocks MEK5-mediated apoptosis in FLT3-ITD mutant-expressing cells and is a valuable research tool for studying oncogenic signaling in acute myeloid leukemia, applicable in both in vitro and in vivo experimental models.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 334949-59-6
• MW: 412.48
• Purity: 97.66%
• Formula: C₂₅H₂₄N₄O₂
• SMILES: C(\NC1=CC(CN(C)C)=CC=C1)(=C\2/C=3C(NC2=O)=CC(C(N)=O)=CC3)/C4=CC=CC=C4
• Target: Apoptosis,MEK,ERK
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.42 mM);DMSO:30 mg/mL (72.73 mM)

Bioactivity

• Target IC50:
  MEK5:4.3 nM|Abl-1:2.1 μM|TGFβRI:1.8 μM|MAPK14 (p38 alpha):3.9 μM|CSF1R (FMS):280 nM|SRC:8.9 μM|JAK3:7.8 μM|c-Kit:550 nM|LCK:390 nM|ERK5:810 nM|RPS6KA6/RSK4:3.2 μM|RPS6KA3/RSK2:4.1 μM
• In Vitro:
  BIX02188 is a potent MEK5 enzyme inhibitor that selectively blocks ERK5 phosphorylation in activated HeLa cells, without impacting the phosphorylation of ERK1/2, JNK, and p38 MAP kinases. Its specificity was further demonstrated in studies with cultured endothelial cells (EC) and bovine lung microvascular endothelial cells (BLMECs), where BIX02188 dose-dependently inhibited BMK1 phosphorylation induced by H2O2 activation, displaying an IC50 of 0.8±1.0 μM. Notably, BIX02188 did not significantly inhibit ERK1/2 and JNK at concentrations ranging from 0.1-10 μM, underscoring its selective action on MEK5-induced BMK1 phosphorylation. Additionally, BIX02188 exhibited strong inhibitory effects on MEK5 and ERK5 activities, with IC50 values of 4.3 nM and 810 nM, respectively, and did not inhibit closely related kinases such as MEK1, MEK2, ERK2, and JNK2. In podocyte studies, pre-incubation with BIX02188 mitigated the pro-fibrotic stimulus-induced proliferation by TGFβ1, highlighting its potential utility in reducing podocyte cell number through the inhibition of Erk5 activation. This comprehensive evaluation demonstrates BIX02188's efficacy and specificity in inhibiting MEK5/ERK5 pathway components, offering valuable insights for therapeutic strategies targeting specific kinase activities.

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

MEK5, Apoptosis, Compound T 1744, Compound T1744, Compound T-1744

Compound Identifiers

PubChem CID

135398492