Ro 5126766

SKU: orb1300300

Description

RO5126766 (CH5126766) is a dual RAF/MEK inhibitor currently in Phase 1 clinical development. It potently inhibits BRAF V600E, BRAF, CRAF, and MEK1 with IC50 values ranging from 8.2 nM to 160 nM. This compound is a valuable research tool for investigating the MAPK pathway in both in vitro and in vivo cancer models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 946128-88-7
• MW: 471.46
• Purity: 98.81% (May vary between batches)
• Formula: C₂₁H₁₈FN₅O₅S
• SMILES: CNS(=O)(=O)Nc1nccc(Cc2c(C)c3ccc(Oc4ncccn4)cc3oc2=O)c1F
• Target: MEK,Raf
• Solubility: 10% DMSO+40% PEG300+5% Tween-80+45% Saline:5 mg/mL (10.61 mM);DMSO:87 mg/mL (184.53 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  B-Raf (V600E):8.2 nM|B-Raf:19 nM|Raf:56 nM|MEK1:160 nM
• In Vivo:
  In an HCT116 (G13D KRAS) mouse xenograft model, CH5126766 (25 mg/kg, p.o.) inhibits ERK signaling output more effectively than a standard MEK inhibitor that induces MEK phosphorylation and has potent antitumor activity. In the HCT116 (K-ras) and COLO205 (B-raf) mutant xenografts, CH5126766 (0.3 mg/kg) causes significant decreases in [18 F]FDG uptake. In the SK-MEL-2 xenograft model, RO5126766 also suppresses the tumor growth.
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• In Vitro:
  In HCT116 KRAS-mutant colorectal cancer cells, CH5126766 significantly reduces the levels of phospho-MEK and phospho-ERK. CH5126766 inhibits RAF kinase by binding to MEK1, and causes MEK to become a dominant negative inhibitor of RAF. In Raf or RAS-mutant cell lines SK-MEL-28, SK-MEL-2, MIAPaCa-2, SW480, HCT116, and PC3 cells, CH5126766 inhibits cell growth with IC50 of 65, 28, 40, 46, and 277 nM, respectively. In two melanoma cell lines with the BRAF V600E or NRAS mutation, RO5126766 induces G1 cell cycle arrest accompanied by up-regulation of the CDK inhibitor p27 and down-regulation of cyclinD1.
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• Cell Research:
  The number of viable cells is determined using the Cell Counting Kit-8 assay according to the manufacturer's instructions. After the incubation of cells for 72 h with the indicated concentrations of various agents, kit reagent WST-8 is added to the medium and incubated for a further 4 h. The absorbance of samples (450 nm) is determined using a scanning multiwell spectrophotometer that serves as an ELISA reader. Cell numbers and viability are also measured using the ViaCount Assay according to the manufacturer's instructions.(Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, Mitogen-activated protein kinase kinase, MAP2K, MAPKK, MEK1, MEK, Inhibitor, C-Raf, CH5126766, CH-5126766, CH 5126766, Avutometinib, B-Raf (V600E), B-Raf, RO5126766, RO-5126766, Ro-5126766, Ro 5126766, Raf kinases, Raf, VS-6766

Compound Identifiers

PubChem CID

16719221