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Fig. 1 · Structure
Cat. No.
A10151
CAS No.
1094614-85-3
Formula
C27H28N4O2
Mol. Weight
440.5

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(E/Z)-BIX 02189

Cat. No. A10151 CAS 1094614-85-3

MEK inhibitor

BIX 02189 is a selective dual MEK5 and ERK5 (or BMK1) kinase inhibitor, with IC50 values of 1.5, 59, 580 and >6200 nM for MEK5, ERK5, TGFbR1 and other closely related kinases respectively.

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Publications for (E/Z)-BIX 02189

2 publications citing this product

  1. Bopei Cui, .et al. , Signal Transduct Target Ther, 2023, Sep 25;8(1):366 PMID: 37743418
  2. Mitsunori Miyazaki, .et al. , FEBS Open Bio, 2017, Mar; 7(3): 424-433 PMID: 28286738
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Biological Activity

Bioactivity / Mechanism

BIX02189 has been used to inhibit MEK5–ERK5 pathway signaling. In PMA-stimulated C2C12 myoblasts, 10 μM BIX-02189 reduced ERK5 phosphorylation without inhibiting ERK1/2 or RSK phosphorylation. This cellular comparison supports pathway inhibition under the tested conditions; it does not establish broad kinase selectivity. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target Activity Value
MEK5 IC50 1.5nM
ERK5 IC50 59nM
TGFβR1 IC50 580nM
MEK1 IC50 >6.2μM
MEK2 IC50 >6.2μM
ERK1 IC50 >6.2μM
JNK2 IC50 >6.2μM
EGFR IC50 >6.3μM
STK16 IC50 >6.3μM

9 targets · Scroll to view more

In Vitro Studies

In C2C12 myoblasts, 10 μM BIX-02189 during a 20-minute exposure to 100 nM PMA partially reduced S6K1 phosphorylation relative to DMSO plus PMA. Basal S6K1 phosphorylation also decreased, and stimulation above the corresponding baseline persisted, limiting interpretation as complete suppression of mTORC1 responsiveness. [1]

In HUVECs exposed to laminar flow, 10 μM BIX02189 reduced induction of HO-1, NQO1 and eNOS protein expression compared with DMSO controls. The reported 16–24-hour experiment used static and flow conditions and showed representative immunoblots from three independent experiments. [2]

ERK5 and S6K1 signaling in PMA-stimulated C2C12 myoblasts

Cell-based study · Murine C2C12 skeletal muscle myoblasts [1]

BIX-02189 reduced PMA-associated ERK5 phosphorylation and partially reduced S6K1 phosphorylation compared with DMSO plus PMA. ERK1/2 and RSK phosphorylation were not inhibited. Basal S6K1 phosphorylation also fell, so stimulation relative to each inhibitor’s own baseline remained; these results do not show complete blockade of PMA responsiveness.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
ERK5 phosphorylation (Thr218/Tyr220)Reported decrease versus DMSO + PMA 46.3% decrease[1]
S6K1 phosphorylation at Thr389 and Thr421/Ser424Reported decrease versus DMSO + PMA 41% (Thr389); 29% (Thr421/Ser424); P < 0.05[1]
ERK1/2 and RSK phosphorylation; basal S6K1 signalingQualitative control and limitation No inhibitory effect on ERK1/2 or RSK phosphorylation; basal S6K1 phosphorylation also diminished[1]

Literature-Reported Treatment Conditions

Treatment concentration
10 μM BIX-02189; 100 nM PMA
Exposure duration
20 min coincubation after 120 min in serum/antibiotic-free medium
Method
Cell treatment followed by phospho-specific immunoblotting
Vehicle
DMSO; final percentage not specified in the adopted locations
Co-treatment
BIX-02189 + PMA; paired unstimulated BIX-02189 condition. U0126, BIM-I and rapamycin were separate comparator conditions.
Reported limits
No E/Z ratio, catalog number or lot reported. Figure 1 n = 4 for S6K1 quantification; not assigned to the ERK5 percentage.
Methods and source locations

Compound reported in the paper: BIX02189; Compound label in the paper: BIX-02189

Results describe the paper’s named BIX02189 material. E/Z ratio, isomer-specific activity and Adooq lot performance are not established.

Figure 1A–C and caption; Results: PMA-induced activation of mTORC1 signaling; Materials and methods: Materials, Antibodies, Cell culture and transfection, Western blotting, Statistical analysis

ERK5 phosphorylation (Thr218/Tyr220): Immunoblotting; author-reported percentage from Results, not digitized from bands. Replicate number/uncertainty for this specific percentage not given there. — Figure 1A–C and caption; Results: PMA-induced activation of mTORC1 signaling; Materials and methods: Materials, Antibodies, Cell culture and transfection, Western blotting, Statistical analysis

S6K1 phosphorylation at Thr389 and Thr421/Ser424: Immunoblot quantification; Figure 1B–C: n = 4 per group, mean ± SE, fold difference versus unstimulated control. Percentages are reported in Results; no uncertainty attached to percentages. — Figure 1A–C and caption; Results: PMA-induced activation of mTORC1 signaling; Materials and methods: Materials, Antibodies, Cell culture and transfection, Western blotting, Statistical analysis

ERK1/2 and RSK phosphorylation; basal S6K1 signaling: Figure 1A and Results; GAPDH loading control, total protein bands, DMSO ± PMA, U0126, BIM-I and rapamycin comparators. No claim of a broad kinase selectivity panel. — Figure 1A–C and caption; Results: PMA-induced activation of mTORC1 signaling; Materials and methods: Materials, Antibodies, Cell culture and transfection, Western blotting, Statistical analysis

Flow-responsive gene expression in HUVECs

Cell-based study · Human umbilical vein endothelial cells (HUVECs), static versus laminar flow (12 dynes/cm²) [2]

In the BIX02189 experiment, flow-induced HO-1, NQO1 and eNOS protein expression was reduced relative to DMSO-treated flow controls. A parallel ERK5-siRNA/control-siRNA comparison reduced flow-induced HO-1 and eNOS and supplies pathway context. These are expression/signaling endpoints, not direct measurements of BIX02189 enzyme potency or vascular protection.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
HO-1, NQO1 and eNOS protein expression under laminar flowQualitative immunoblot result Flow-induced expression inhibited by BIX02189; representative of three independent experiments[2]

Literature-Reported Treatment Conditions

Treatment concentration
10 μM
Exposure duration
16–24 h under flow in the presence of compound (Figure 2B caption)
Method
Laminar-flow exposure followed by immunoblotting
Vehicle
DMSO comparator; percentage not specified
Co-treatment
No additional drug; flow is the experimental stimulus
Reported limits
Exact pretreatment interval for Figure 2B is not specified in its caption; Results calls it pretreatment. No numeric effect size or inferential statistics supplied for these representative blots.
Methods and source locations

Compound reported in the paper: BIX02189; Compound label in the paper: BIX02189

Results describe the paper’s named BIX02189 material. E/Z ratio, isomer-specific activity and Adooq lot performance are not established.

Figure 2A–B and caption; Results: ERK5 Is Required for Laminar Flow-induced Nrf2-dependent Gene Expression; Experimental Procedures: Cell Culture, Reagents, Statistical Analysis

HO-1, NQO1 and eNOS protein expression under laminar flow: Figure 2B immunoblotting, with static and flow conditions in both DMSO and BIX02189 groups; pERK5, total ERK5 and tubulin shown. Figure 2A provides separate ERK5-siRNA validation with control siRNA and β-actin. — Figure 2A–B and caption; Results: ERK5 Is Required for Laminar Flow-induced Nrf2-dependent Gene Expression; Experimental Procedures: Cell Culture, Reagents, Statistical Analysis

In Vivo Studies

In male C57BL/6 mice, BIX02189 at 10 mg/kg intraperitoneally reduced nuclear Nrf2 localization in thoracic aortic endothelium relative to 25% DMSO vehicle. This was a qualitative localization endpoint; treatment timing, repeat frequency and animal number were not specified in the reported animal methods or figure caption. [2]

In an STZ mouse model, BIX02189 co-treatment was associated with higher fasting glucose, greater body-weight loss and increased pancreatic apoptosis readouts compared with STZ alone. This adverse, model-specific result does not support general therapeutic benefit or establish an exclusively ERK5-mediated effect. [3]

Nrf2 localization in mouse aortic endothelium

Animal study · Six-week-old male C57BL/6 mice; thoracic aortic endothelium [2]

En face immunofluorescence images showed less nuclear Nrf2 localization after BIX02189 than after vehicle. VE-cadherin and Topro3 identify endothelial junctions and nuclei. This qualitative localization experiment does not measure atherosclerotic lesions, therapeutic benefit or a quantitative inhibition percentage.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Endothelial nuclear Nrf2 localizationQualitative immunofluorescence Nuclear localization reduced relative to vehicle[2]

Conditions shared by the study groups

Route
Intraperitoneal
Vehicle
25% DMSO
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
BIX02189 versus vehicle
10 mg/kg		Same volume of 25% DMSOReduced nuclear Nrf2 localization in aortic endothelial staining relative to vehicle[2]
BIX02189 versus vehicle
Model: Six-week-old male C57BL/6 mice; thoracic aortic endothelium
Reported limits: Dose-to-sampling interval, repeat frequency, course and animal n are not specified in the read animal methods/Figure 7 caption.
Methods and source locations

Compound reported in the paper: BIX02189; Compound label in the paper: BIX02189

Results describe the paper’s named BIX02189 material. E/Z ratio, isomer-specific activity and Adooq lot performance are not established.

Figure 7 and caption; Results: ERK5 Mediates Flow-induced Nrf2 Nuclear Translocation in Vivo; Experimental Procedures: Animal Experiments

Endothelial nuclear Nrf2 localization: Figure 7 en face confocal imaging; anti-Nrf2, VE-cadherin and Topro3 staining. No numerical group comparison or animal n given in adopted locations. — Figure 7 and caption; Results: ERK5 Mediates Flow-induced Nrf2 Nuclear Translocation in Vivo; Experimental Procedures: Animal Experiments

BIX02189 versus vehicle · Figure 7 and caption; Results: ERK5 Mediates Flow-induced Nrf2 Nuclear Translocation in Vivo; Experimental Procedures: Animal Experiments

Adverse response to BIX02189 in an STZ mouse model

Animal study · Eight-week-old male C57BL/6J mice, streptozotocin-associated hyperglycemia [3]

Co-treatment with BIX02189 increased fasting blood glucose, body-weight loss, cleaved PARP-1/caspase-3 and islet TUNEL positivity compared with STZ alone. BIX02189-only controls were included. These compound-associated findings are specific to the STZ model; Figure 1C does not show a clear reduction of pancreatic phospho-ERK5/total ERK5, so exclusive on-target attribution is not established.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Fasting blood glucose and body weight over 6 daysDirection and reported comparison Higher glucose and greater weight loss with STZ + BIX02189 versus STZ; #p < 0.05[3]
Pancreatic cleaved PARP-1/caspase-3 and TUNEL-positive islet cellsQualitative direction with reported significance Increased versus STZ alone; Figure 1C–D **p < 0.01 annotations[3]

Conditions shared by the study groups

Route
Intraperitoneal
Frequency
BIX02189 every 2 days; STZ is described as a single injection in Methods
Treatment course
6-day BIX02189 experiment
Vehicle
BIX02189 in 100 μL saline (Methods); caption describes vehicle as citrate buffer
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
STZ + BIX02189 versus STZ alone
BIX02189 10 mg/kg body weight; STZ 150 mg/kg body weight		STZ alone; Figure 1 also includes vehicle-only and BIX02189-only groupsHigher fasting glucose and greater body-weight loss than STZ alone; increased pancreatic apoptosis readouts[3]
STZ + BIX02189 versus STZ alone
Model: Eight-week-old male C57BL/6J mice, streptozotocin-associated hyperglycemia
Reported limits: No BIX02189 E/Z composition. Methods/caption differ in vehicle wording; matched solvent composition for each group is not fully detailed. No exact graph-derived values adopted.
Methods and source locations

Compound reported in the paper: BIX02189; Compound label in the paper: BIX02189

Results describe the paper’s named BIX02189 material. E/Z ratio, isomer-specific activity and Adooq lot performance are not established.

Figure 1A–D and caption; Results: ERK5 inhibition enhanced STZ-induced hyperglycemia and pancreatic cell death; Materials and methods: Reagents and antibodies, Animal experiments, Immunostaining and TUNEL assay, Statistical analysis

Fasting blood glucose and body weight over 6 days: Figure 1A–B time courses; means ± SDs, n = 10 mice as caption reports; ANOVA. No exact values inferred from plots. — Figure 1A–D and caption; Results: ERK5 inhibition enhanced STZ-induced hyperglycemia and pancreatic cell death; Materials and methods: Reagents and antibodies, Animal experiments, Immunostaining and TUNEL assay, Statistical analysis

Pancreatic cleaved PARP-1/caspase-3 and TUNEL-positive islet cells: Immunoblotting and TUNEL/insulin/nuclear staining; figure includes vehicle, BIX02189 alone, STZ and STZ + BIX02189. Specific n for panel 1D is not stated in its caption; no n borrowed from another figure. — Figure 1A–D and caption; Results: ERK5 inhibition enhanced STZ-induced hyperglycemia and pancreatic cell death; Materials and methods: Reagents and antibodies, Animal experiments, Immunostaining and TUNEL assay, Statistical analysis

STZ + BIX02189 versus STZ alone · Figure 1A–D and caption; Results: ERK5 inhibition enhanced STZ-induced hyperglycemia and pancreatic cell death; Materials and methods: Reagents and antibodies, Animal experiments, Immunostaining and TUNEL assay, Statistical analysis

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 1094614-85-3
Applications MEK inhibitor
Formula C27H28N4O2
Molecular Weight 440.5
SMILES
CN(C)CC1=CC(=CC=C1)N/C(=C\2/C3=C(C=C(C=C3)C(=O)N(C)C)NC2=O)/C4=CC=CC=C4

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO Warmed: 56 mg/mL (127.11 mM)
Water Insoluble
Ethanol 75 mg/mL (170.24 mM)

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

In Vivo Preparation

Concentration
9 mg/mL
Vehicle
2% DMSO+30% PEG 300+5% Tween 80+ddH2O

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Miyazaki M, Takemasa T. TSC2/Rheb signaling mediates ERK-dependent regulation of mTORC1 activity in C2C12 myoblasts FEBS open bio (2017). PMID: 28286738 DOI: 10.1002/2211-5463.12195 Source material
  2. [2] Kim M, Kim S, Lim JH, et al. Laminar flow activation of ERK5 protein in vascular endothelium leads to atheroprotective effect via NF-E2-related factor 2 (Nrf2) activation The Journal of biological chemistry (2012). PMID: 23043106 DOI: 10.1074/jbc.m112.381509 Source material
  3. [3] Nam DH, Han JH, Lim JH, et al. CHOP Deficiency Ameliorates ERK5 Inhibition-Mediated Exacerbation of Streptozotocin-Induced Hyperglycemia and Pancreatic β-Cell Apoptosis Molecules and cells (2017). PMID: 28681594 DOI: 10.14348/molcells.2017.2296 Source material

Publications

2 publications citing this product

  1. Bopei Cui, .et al. , Signal Transduct Target Ther, 2023, Sep 25;8(1):366 PMID: 37743418
  2. Mitsunori Miyazaki, .et al. , FEBS Open Bio, 2017, Mar; 7(3): 424-433 PMID: 28286738

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