Avutometinib (Ro 5126766) 是一种有效的双重 MEK/RAF 抑制剂，抑制 BRAF^V600E，CRAF, MEK，和 BRAF，IC₅₀ 分别为 8.2 nM, 56 nM, 160 nM 和 190 nM。

Avutometinib (Ro 5126766) is a first-in-class dual MEK/RAF inhibitor that allosterically inhibits BRAF, CRAF, MEK, and BRAF (IC 50 : 8.2, 56, 160 nM, and 190 nM, respectively).

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MEK 160 nM (IC50) BRaf 8.2 nM (IC50

Avutometinib (Ro 5126766) is an allosteric inhibitor that binds directly to MEK and prevents its phosphorylation by RAF through the formation of a stable RAF-MEK complex. Ro 5126766 inhibits both the phosphorylation of MEK by RAF and the activation of ERK by MEK. In cell-free MEK and RAF kinase assays, Avutometinib effectively inhibits activation of ERK2 by MEK1 with an IC50 of 160 nM (SD=±0.043) and inhibits the phosphorylation of MEK1 protein by BRAF (IC50=190 nM, SD=±0.003), BRAF (IC50=8.2 nM, SD=±0.0015), and CRAF (IC50=56 nM, SD=±0.016). Avutometinib effectively inhibits both MEK and ERK phosphorylation in a panel of human tumor cell lines including KRAS / HRAS and BRAF mutant cell lines and KRAS / HRAS and BRAF wild-type cells. In order to investigate whether the mevalo

In KRAS-mutant xenograft models, Avutometinib (Ro 5126766) inhibits growth and causes tumor regressions more effectively than another allosteric MEK inhibitor, PD0325901. Preclinical data from a series of human tumor mouse xenograft models indicates an ED 50 for Ro 5126766 of 0.03 to 0.23 mg/kg and an ED 90 of 0.15 to 1.56 mg/kg. These effective doses are associated with target trough concentrations of 17 to 133 ng/L and 87 to 901 ng/mL, respectively. . In this experiment, Avutometinib or PD0325901 is administrated at their maximum tolerated dose (MTD) in the HCT116 model (1.5 and 25 mg/kg, respectively). These doses inhibit pERK and ERK signaling output at similar degrees in the tumors from the drug-treated mice at 4 hours from the first drug administration. Moreover, in HCT116 models, the ED 50 for Avutometinib and PD0325901 are 0.056 an

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Powder -20°C 3 years；4°C 2 years

[1]. Martinez-Garcia M, et al. First-in-human, 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. Clin Cancer Res. 2012 Sep 1;18(17):4806-19.
[2]. Iizuka-Ohashi M, et al. Blockage of the mevalonate pathway overcomes the apoptotic resistance to MEK inhibitors with suppressing the activation of Akt in cancer cells. Oncotarget. 2018 Apr 13;9(28):19597-19612.

In Vitro: DMSO : 125 mg/mL (265.13 mM; Need ultrasonic)配制储备液