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RO5126766 (VS-6766)

Cat. No. M10369
RO5126766 (VS-6766) Structure
Synonym:

CH5126766; VS 6766

Size Price Availability Quantity
10mg USD 226  USD226 In stock
50mg USD 689  USD689 In stock
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Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
Biological Activity

RO5126766 (CH5126766, VS 6766) is a first-in-class dual MEK/RAF inhibitor with IC50 values of 8.2 nM, 19 nM, 56 nM and 160 nM for BRAF V600E, BRAF, CRAF and MEK1, respectively. 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 vivo, RO5126766 (25 mg/kg, p.o.) inhibits ERK signaling output more effectively in an HCT116 (G13D KRAS) mouse xenograft model 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 [18F]FDG uptake.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 471.46
Formula C21H18FN5O5S
CAS Number 946128-88-7
Purity >98%
Solubility DMSO 90 mg/mL
Storage at -20°C
References

[1] Mahiro Iizuka-Ohashi, et al. Oncotarget. Blockage of the mevalonate pathway overcomes the apoptotic resistance to MEK inhibitors with suppressing the activation of Akt in cancer cells

[2] Makoto Wada, et al. PLoS One. The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells

[3] Tetyana Tegnebratt, et al. EJNMMI Res. [18 F]FDG-PET imaging is an early non-invasive pharmacodynamic biomarker for a first-in-class dual MEK/Raf inhibitor, RO5126766 (CH5126766), in preclinical xenograft models

[4] Nobuya Ishii, et al. Cancer Res. Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity

[5] Maria Martinez-Garcia, et al. Clin Cancer Res. phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: RO5126766 (VS-6766), CH5126766; VS 6766 supplier, MEK, inhibitors

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