CI-1040

SKU: orb1305479

Description

CI-1040

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 212631-79-3
• MW: 478.66
• Purity: 99.64%
• Formula: C₁₇H₁₄ClF₂IN₂O₂
• SMILES: Fc1ccc(C(=O)NOCC2CC2)c(Nc2ccc(I)cc2Cl)c1F
• Target: Apoptosis,MEK
• 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 o 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 o 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 inhibi 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 tha the concentration required to inhibi 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 treate 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 o the Samples, propidium iodide (50 μg/ml) and RNase (30 units/ml) were added to the pellets for 20 min at 37℃. After filtration, Samples were analyzed by flow cytometry.
• Animal Research:
  Tumor fragments (approximately 3 mm^3 in size) were implanted Subcutaneously int the right axillae of CD2F1 Male mice (colon 26 studies) or f Male nude mice (HT-29 studies) 4–6 weeks old. Treatment was administered by gavage or intraperitoneally and was initiated eithe 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 a the time required for treated and control tumors, respectively to Each 750 mg (colon 26) or to Each 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