Cobimetinib

SKU: orb1303987

Description

Cobimetinib (GDC-0973) is a potent and selective oral MEK1 inhibitor (IC50=4.2 nM). It demonstrates antitumor efficacy by suppressing proliferation and promoting apoptosis in tumor cells, as validated in both cellular assays and in vivo xenograft models for cancer research.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 934660-93-2
• MW: 531.31
• Purity: 99.98%
• Formula: C₂₁H₂₁F₃IN₃O₂
• SMILES: C(=O)(C1=C(NC2=C(F)C=C(I)C=C2)C(F)=C(F)C=C1)N3C[C@](O)(C3)[C@@H]4CCCCN4
• Target: MEK,Apoptosis
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.76 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:44 mg/mL (82.81 mM);DMSO:84.17 mg/mL (158.42 mM)

Bioactivity

• Target IC50:
  MEK:0.9 nM
• In Vivo:
  METHODS: To assay antitumor activity in vivo, Cobimetinib (1-10 mg/kg) was administered orally to mice bearing A375.X1 or NCI-H2122 xenografts once daily for 21 days. RESULTS: In the A375.X1 BRAFV600E mutant melanoma xenograft model, treatment with a dose of Cobimetinib greater than 3 mg/kg resulted in an intense TGI, and in the NCI-H2122 KRASG12C mutant NSCLC xenograft model, treatment with up to 5 mg/kg Cobimetinib resulted in a moderate TGI, and treatment with 10 mg/kg approached tumor arrest.
• In Vitro:
  METHODS: A panel of BRAF-mutant, RAS-mutant, or wild-type cell lines were treated with Cobimetinib for 96 h and cell viability was measured by Cell Death Detection ELISA Plus kit. RESULTS: Cobimetinib showed potent cellular potency in multiple tumor types, particularly in BRAF or KRAS mutant cancer cell lines. In a subset of tumor cell lines, 80% of BRAF-mutant lines (both V600E and non-V600E mutations) were sensitive to Cobimetinib (EC50<1 µmol/L), 54% of lines harboring KRAS or NRAS-carrying mutations were sensitive, and the remaining 35% of lines were sensitive. METHODS: NB cell lines IMR-32, SHEP, and IMR-5 were treated with Cobimetinib (1 µM) for 4 h, and target protein expression levels were measured by Western Blot. RESULTS: Cobimetinib treatment induced dephosphorylation of c-RAF and ERK and increased phosphorylation of MEK.
• Cell Research:
  Cells are plated in quadruplicate at a density of 3,000 per well in 384-well plates in normal growth medium and allowed to adhere overnight. Compounds are added in 10 concentrations based on a 3-fold dilution series. Cell viability is measured 72 h later using the CellTiter-Glo Luminescent Cell Viability Assay.(Only for Reference)

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

XL 518, XL518, XL-518, RG 7420, RG7420, RG-7420, Mitogen-activated protein kinase kinase, inhibit, Inhibitor, GDC 0973, GDC0973, GDC-0973, MAP2K, MEK1, MEK, MAPKK, Apoptosis, Cobimetinib

Compound Identifiers

PubChem CID

16222096