Selumetinib

SKU: orb1300969

Description

Selumetinib

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 606143-52-6
• MW: 457.68
• Purity: 99.90%
• Formula: C₁₇H₁₅BrClFN₄O₃
• SMILES: CN1C=NC2=C(F)C(NC3=CC=C(Br)C=C3Cl)=C(C=C12)C(=O)NOCCO
• Target: MEK,Apoptosis,ERK
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:81.7 mg/mL (178.51 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.37 mM)

Bioactivity

• Target IC50:
  MEK:12 nM|ERK1/2 phosphorylation:10.3 nM (Malme-3M cells)|MEK1:14 nM (cell free)
• In Vivo:
  METHODS: To assay antitumor activity in vivo Selumetinib (50 mg/kg, 0.5% hydroxypropyl methyl cellulose and 0.1% Tween 80) was administered by gavage to athymic nu/nu mice bearing MDA-MB-231-LM2 xenografts five times per week for three weeks. For three weeks. Results: In mice treated with Selumetinib, lung metastases were inhibited and tumor cells reversed from a mesenchymal phenotype to an epithelial phenotype.
• In Vitro:
  METHODS: TNBC cell lines MDA-MB-231, MDA-MB-468, SUM149, SUM190, KPL-4, and MDA-IBC-3 were treated with Selumetinib (0-100 µM) for 72 h, and cell viability was measured by WST-1 assay. Results: In MDA-MB-468, SUM190, KPL-4 and MDA-IBC-3 cells the IC50 was above 20 µM, and in MDA-MAB-231 and SUM149 cells the IC50 Values were 8.6 µM and 10 µM, respectively METHODS: Breast cancer cells HCC-1937 and MDA-MB-231 were treated with Selumetinib (1-50 µM) for 24 h, an the cell cycle was detected by Flow cytometry. Results: Selumetinib triggered apoptosis and G1 phase block in a dose-dependent manner.
• Cell Research:
  Primary HCC cells were plated at a density of 2.0 × 10^4 per well in growth medium. After 48 h in growth medium the cell monolayer was rinsed twice with MEM. Cells were treated with various concentration of AZD6244 (0, 0.5, 1.0, 2.0, 3.0, and 4.0 μMol/L) for 24 or 48 h. Cell viability was determined b the MTT assay. Cell proliferation was assayed using a bromodeoxyuridine kit as described b the manufacturer. Experiments were repeated at least thrice, an the data were expressed as mean ± SE.
• Animal Research:
  HT-29 human colon carcinoma or BxPC3 human pancreatic tumor fragments were implanted s.c. in the flank of nude mice and allowed to grow to 100 to 150 mg. Mice (n = 10 per group) were andomized to treatment groups to receive Vehicle (10 L/kg and 10% ethanol/10% cremophor EL/80% D5W) or ARRY-142886 (10, 25, 50, or 100 mg/kg, oral, BID) on days 1 to 21. Tumors [(W^2 × L) / L] were measured twice weekly. Tumor growth Inhibition was calculated as 1 (tumor sizetreated / tumor siz Vehicle) on Each measurement day. Four hours afte the last dose on day 21, three mice per group were euthanized to evaluate pharmacokinetic/pharmacodynamic responses. Tumors were excised and flash frozen. Homogenates were analyzed for phospho-ERK1/2 and ERK1/2 expression by Western blotting as described above. Fo the HT-29 study, monitoring of tumor regrowth was continued fo the remaining seven mice per group until tumors reached 1,000 mm^3, when mice would be sacrificed. There were two BxPC3 tumor xenograft studies. Fo the first study, one group of mice was treated wit the clinical s andard of care, gemcitabine, at 160 mg/kg, i.p., every 3rd day for a total of four doses. This dose was determined to b the maximum tolerated dose for gemcitabine in the BxPC3 model on this dosing schedule. To evaluate whether previously treated tumors would be refractory to a second cycle of treatment, a second BxPC3 xenograft study was carried out. Mice were treated with Vehicle or ARRY-142886 at 25 or 50 mg/kg, BID, for 21 days. Treatment was stopped and tumors were allowed to grow for an additional 7 days before treatment resumed for a Other 21-day cycle.

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

inhibit, Mitogen-activated protein kinase kinase, ERK2, ERK1, MEK, MEK1, MAPKK, MAP2K, Inhibitor, ARRY 142886, ARRY142886, ARRY-142886, AZD 6244, AZD6244, AZD-6244, Apoptosis, Selumetinib

Compound Identifiers

PubChem CID

10127622