CI-1040

SKU: orb1305479

Description

CI-1040 (PD184352) is a potent and selective, ATP-noncompetitive inhibitor of MEK1 and MEK2 with an IC50 of 17 nM. This compound is a valuable research tool for investigating the MAPK/ERK pathway in both in vitro cellular assays and in vivo models of cancer and other proliferative diseases.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 212631-79-3
• MW: 478.66
• Purity: 99.64% (May vary between batches)
• Formula: C₁₇H₁₄ClF₂IN₂O₂
• SMILES: Fc1ccc(C(=O)NOCC2CC2)c(Nc2ccc(I)cc2Cl)c1F
• Target: MEK,Apoptosis
• Solubility: Ethanol:12 mg/mL (25.07 mM);DMSO:125 mg/mL (261.15 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.18 mM)

Bioactivity

• Target IC50:
  MEK2:17 nM (cell free)|MEK1:17 nM (cell free)
• In Vivo:
  The tumors were excised at 1 hour and 6 hours after treatment with PD 184352 (150 mg/kg, i.p. or p.o.). Treatment with PD 184352 completely suppressed MAPK phosphorylation by either route of administration for at least 6 hours. MAPK phosphorylation returned at 12 hours after dosing and attained control levels by 24 hours . In vivo, the systemic administration of the MEK inhibitor CI-1040 reduced adenoma formation to a third and significantly restored lung structure. The proliferation rate of lung cells of mice treated with CL-1040 was decreased without any obvious effects on the differentiation of pneumocytes .
• In Vitro:
  PD 184352 (CI-1040) also substantially reduced steady-state levels of phosphorylated MAPK (pMAPK) in a diverse panel of tumor lines grown in the presence of serum. Treatment of colon 26 cells for 1 hour with 1 μM PD 184352 produced a reduction of pMAPK levels of more than 75%. Treatment of colon 26 cells with 10 μM PD 184352 did not inhibit the phosphorylation of Jun kinase, p38 kinase or AKT . The IC50 for inhibition of MKK1 by PD 184352 was 0.3 μM, 15-fold higher than the concentration required to inhibit the EGF-induced activation of ERK2 in Swiss 3T3 cells. The activation of MKK1 in cells was inhibited by 50% at 2 nM PD 184352 . CI-1040 induced apoptosis and inhibited proliferation in U-937 cells in a dose and time-dependent manner. CI-1040 induced a significant increase in PUMA mRNA and protein levels. Knockdown of PUMA by PUMA siRNA transfection inhibited CI-1040-induced apoptosis and proliferation inhibition in U-937 cells .
• Cell Research:
  Cells were planted seeded in T-75 cm2 flasks and treated the next day for 24 h with either DMSO or PD 184352. Single-cell suspensions were collected, and pellets were fixed in ice-cold ethanol (70%) for 30 min. After centrifugation of the samples, propidium iodide (50 μg/ml) and RNase (30 units/ml) were added to the pellets for 20 min at 37 °C. After filtration, samples were analyzed by flow cytometry .
• Animal Research:
  Tumor fragments (approximately 3 mm^3 in size) were implanted subcutaneously into the right axillae of CD2F1 male mice (colon 26 studies) or female nude mice (HT-29 studies) 4–6 weeks old. Treatment was administered by gavage or intraperitoneally and was initiated either the day after tumor implantation (colon 26) or when tumors reached approximately 200 mg in size (HT-29). PD 184352 was prepared in a vehicle of 10% Cremophore EL, 10% ethanol and 80% water. Tumor size was evaluated periodically by caliper measurements, generally three times per week. Percent tumor growth inhibition was calculated as [(T–C)/number of days of treatment] × 100, with T and C being defined as the time required for treated and control tumors, respectively, to reach 750 mg (colon 26) or to reach twofold growth (HT-29) .

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

CI1040, CI-1040, CI 1040, Apoptosis, Mitogen-activated protein kinase kinase, PD 184352, PD184352, PD-184352, inhibit, Inhibitor, MAPKK, MEK2, MEK1, MEK, MAP2K

Compound Identifiers

PubChem CID

6918454