Fig. 1 · Structure

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Binimetinib (MEK162, ARRY-438162)

MEK1/2 inhibitor

MEK162 (ARRY-438162) is a potent, selective, ATP uncompetitive inhibitor of MEK1/2.

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Publications for Binimetinib

3 publications citing this product

  1. S Shahab, .et al. , J Neuropathol Exp Neurol, 2020, Jul 1;79(7):746-753 PMID: 32472116
  2. Seidel D, .et al. , Biosens Bioelectron, 2019, Jan 1;123:185-194 PMID: 30201332
  3. Alquezar C, .et al. , Eur Neuropsychopharmacol, 2015, Mar;25(3):386-403 PMID: 25624003

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Biological Activity

Bioactivity / Mechanism

MEK162 (binimetinib) suppresses downstream ERK1/2 phosphorylation in pancreatic cancer cells. At 100 nM, short-term pathway inhibition occurred in both growth-sensitive and growth-resistant models; suppression at 24–48 h was maintained in PANC 02.03 and MIAPaCa-2 but not YAPC or CFPAC1. [1]

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

Target & Activity

Target Activity Value
MEK 12 nM

In Vitro Studies

Growth inhibition varied across 29 pancreatic cancer cell lines. Reported IC50 values included 0.0092 μM in MIAPACA-2, 5.0654 μM in YAP-C and >10 μM in PATU-8988T. KRAS mutation presence alone did not distinguish sensitivity (P = 0.5271). These are cellular growth endpoints, not biochemical potency values. [1]

Growth inhibition across pancreatic cancer cell lines

Cell-based study · 29 human pancreatic cancer cell lines [1]

Cell-count-based growth sensitivity varied widely; KRAS mutation presence alone did not distinguish response.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Growth inhibition in PANC 05.04IC50 0.0027 μM[1]
Growth inhibition in MIAPACA-2IC50 0.0092 μM[1]
Growth inhibition in YAP-CIC50 5.0654 μM[1]
Growth inhibition in CFPAC1IC50 8.5259 μM[1]
Growth inhibition in PATU-8988TIC50 >10 μM[1]
Mutant versus wild-type KRAS growth-inhibition IC50 comparisonP value P = 0.5271[1]

Literature-Reported Treatment Conditions

Treatment concentration
10 μM to 0.0001 μM, tenfold serial dilutions
Exposure duration
Treatment 24 h after seeding; cells counted 6 days after seeding (approximately 5 days of exposure)
Method
Cell counting with Coulter-Z1; percent generational inhibition relative to untreated cells
Reported limits
Vehicle and tested material supplier/form characterization are not specified in the retrieved methods. Individual IC50 uncertainty is not tabulated. Experiments performed at least twice, wells seeded in duplicate.
Methods and source locations

Compound reported in the paper: MEK162 (binimetinib); Compound label in the paper: MEK162

Reported experimental material; no current AdooQ lot validation or clinical efficacy inference.

Table 1; Figure 1A–C; Methods: Proliferation assays; Results: Association of specific KRAS mutations with sensitivity to MEK inhibition

Growth inhibition in PANC 05.04: Cell-count growth inhibition; Table 1 numerical value, units established by Figure 1A and assay concentration range — Table 1, PANC 05.04 row; Figure 1A caption

Growth inhibition in MIAPACA-2: Cell-count growth inhibition; Table 1 numerical value, units established by Figure 1A and assay concentration range — Table 1, MIAPACA-2 row; Figure 1A caption

Growth inhibition in YAP-C: Cell-count growth inhibition; Table 1 numerical value, units established by Figure 1A and assay concentration range — Table 1, YAP-C row; Figure 1A caption

Growth inhibition in CFPAC1: Cell-count growth inhibition; Table 1 numerical value, units established by Figure 1A and assay concentration range — Table 1, CFPAC1 row; Figure 1A caption

Growth inhibition in PATU-8988T: Cell-count growth inhibition; Table 1 numerical value, units established by Figure 1A and assay concentration range — Table 1, PATU-8988T row; Figure 1A caption

Mutant versus wild-type KRAS growth-inhibition IC50 comparison: Comparison of average IC50; wild-type n = 4, mutant n = 25 cell lines — Figure 1C and caption; Results: Association of specific KRAS mutations

ERK pathway inhibition and model-dependent persistence

Cell-based study · Short-term pancreatic cancer cell-line panel; longer-term comparison of PANC 02.03, MIAPaCa-2, YAPC and CFPAC1 [1]

ERK1/2 phosphorylation decreased after short exposure, including in growth-insensitive lines. Persistent inhibition differed between sensitive and resistant models.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
ERK1/2 phosphorylation after 10 minqualitative Reduced in both growth-sensitive and growth-resistant lines[1]
ERK1/2 phosphorylation after 24 and 48 hqualitative Sustained suppression in PANC 02.03 and MIAPaCa-2; suppression not maintained in YAPC and CFPAC1[1]
AKT and S6 phosphorylation after 10 minqualitative No detected change[1]

Literature-Reported Treatment Conditions

Treatment concentration
100 nM
Exposure duration
10 min; 24 and 48 h
Method
Western blotting compared with untreated controls; total target protein and loading controls included
Reported limits
Vehicle not specified. Representative blots from experiments performed in duplicate; no quantitative effect size extracted.
Methods and source locations

Compound reported in the paper: MEK162 (binimetinib); Compound label in the paper: MEK162

Reported experimental material; no current AdooQ lot validation or clinical efficacy inference.

Figures 4A–C and 5A–C; Methods: Western blots; Results: Downstream mediators of RAS signalling determine duration of MEK inhibition

ERK1/2 phosphorylation after 10 min: Phospho-ERK1/2 T202/Y204 Western blots; untreated controls, total ERK1/2 and β-actin — Figure 4A; Results: Downstream mediators; Methods: Western blots

ERK1/2 phosphorylation after 24 and 48 h: Western blot; untreated controls, total ERK1/2 and α-tubulin — Figure 5A; Results: Downstream mediators

AKT and S6 phosphorylation after 10 min: Western blot with total protein/loading controls; representative blots, duplicate experiments — Figure 4B–C; Results: Downstream mediators

In Vivo Studies

In AT/RT flank xenografts, oral binimetinib reduced CHLA-06 tumor-volume growth (p < 0.005), while the CHLA-266 volume trend was not significant (p = 0.066); terminal tumor mass decreased in both models. In separate intracranial CHLA-06 experiments, the authors reported no survival improvement, with data not shown. [2]

Binimetinib in AT/RT flank xenografts

Animal study · Nude mice bearing CHLA-06 or CHLA-266 flank xenografts [2]

CHLA-06 tumor volume growth was reduced significantly; the CHLA-266 volume trend was not significant. Terminal tumor mass was lower in both models.

Conditions shared by the study groups

Route
Oral
Frequency
Twice daily, 5 days/week per Methods
Treatment course
Approximately 2 weeks; Figure 4 caption specifies 14 days, with panel C specimens described after 15 days
Vehicle
1% carboxymethylcellulose; general Drug Treatments section additionally specifies 0.5% Tween80
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
CHLA-06 flank xenograft
10 mg/kg
Vehicle aloneTumor-volume comparison: p < 0.005 (multiple comparison t-test, Holm–Sidak). Terminal tumor mass lower than vehicle (p < 0.05).[2]
CHLA-266 flank xenograft
10 mg/kg
Vehicle aloneTumor-volume comparison: p = 0.066 (not statistically significant) (multiple comparison t-test, Holm–Sidak). Terminal tumor mass lower than vehicle (p < 0.05).[2]
CHLA-06 flank xenograft
Model: Nude mice; CHLA-06 flank tumors
Reported limits: Exact administration-day calendar is not reconciled between methods and caption; no exact volume/mass effect size extracted.
CHLA-266 flank xenograft
Model: Nude mice; CHLA-266 flank tumors
Reported limits: Exact administration-day calendar is not reconciled between methods and caption; no exact volume/mass effect size extracted.
Methods and source locations

Compound reported in the paper: MEK162 (binimetinib); Compound label in the paper: Binimetinib

Reported experimental material; no current AdooQ lot validation or clinical efficacy inference.

Figure 4A–D; Results: Binimetinib Treatment Decreases Tumor Growth In Vivo in Heterotopic Models But Not in Orthotopic Models; Methods: Drug Treatments, Xenograft Tumors, Statistical Analysis

CHLA-06 flank xenograft · Figure 4B–D and caption; Results: in vivo; Methods: Drug Treatments and Xenograft Tumors

CHLA-266 flank xenograft · Figure 4A,D and caption; Results: in vivo; Methods: Drug Treatments and Xenograft Tumors

No detected survival benefit in intracranial AT/RT xenografts

Animal study · Mice bearing intracranial CHLA-06 AT/RT xenografts [2]

The authors reported no survival difference from vehicle in two separate experiments; data were not shown.

Conditions shared by the study groups

Route
Oral (explicit in Methods for the 30 mg/kg regimen)
Frequency
10 mg/kg: 5 days/week, within-day frequency not specified in the orthotopic Results sentence; 30 mg/kg: twice daily, 4 days/week
Treatment course
30 mg/kg regimen began the day after implantation per Methods; treatment continued until signs of distress; exact duration not given
Vehicle
General in vivo formulation: 1% carboxymethylcellulose with 0.5% Tween80
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
CHLA-06 intracranial xenografts
10 mg/kg or 30 mg/kg, in separate reported experiments
VehicleNo detected survival difference in two separate experiments (data not shown).[2]
CHLA-06 intracranial xenografts
Model: Intracranial CHLA-06 AT/RT xenografts in mice
Reported limits: No survival curves, effect estimates or statistical test details; cohort wording does not establish group-specific n. Mouse strain/sex/age for the intracranial design are not specified in the located text.
Methods and source locations

Compound reported in the paper: MEK162 (binimetinib); Compound label in the paper: Binimetinib

Reported experimental material; no current AdooQ lot validation or clinical efficacy inference.

Results: Binimetinib Treatment Decreases Tumor Growth In Vivo in Heterotopic Models But Not in Orthotopic Models; Methods: Xenograft Tumors; Discussion

CHLA-06 intracranial xenografts · Results: final paragraph of in vivo subsection; Methods: Drug Treatments and Xenograft Tumors

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 606143-89-9
Applications MEK1/2 inhibitor
Formula C17H15BrF2N4O3
Molecular Weight 440
Synonyms ARRY-162; MEK-162; ARRY-438162
SMILES
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)F)C(=O)NOCCO

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO Warmed: 86 mg/mL (194.91 mM)
Water Insoluble
Ethanol Insoluble

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
28 mg/mL
Vehicle
1% CMC+0.5% Tween-80

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] Hamidi H, Lu M, Chau K, et al. KRAS mutational subtype and copy number predict in vitro response of human pancreatic cancer cell lines to MEK inhibition British journal of cancer (2014). PMID: 25167228 DOI: 10.1038/bjc.2014.475 Source material
  2. [2] Shahab S, Rubens J, Kaur H, et al. MEK Inhibition Suppresses Growth of Atypical Teratoid/Rhabdoid Tumors Journal of neuropathology and experimental neurology (2020). PMID: 32472116 DOI: 10.1093/jnen/nlaa042 Source material

Publications

3 publications citing this product

  1. S Shahab, .et al. , J Neuropathol Exp Neurol, 2020, Jul 1;79(7):746-753 PMID: 32472116
  2. Seidel D, .et al. , Biosens Bioelectron, 2019, Jan 1;123:185-194 PMID: 30201332
  3. Alquezar C, .et al. , Eur Neuropsychopharmacol, 2015, Mar;25(3):386-403 PMID: 25624003

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