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RO5126766(CH5126766) Sale

(Synonyms: Ro 5126766; CH5126766) 目录号 : GC12406

A dual inhibitor of MEK1 and Raf kinases

RO5126766(CH5126766) Chemical Structure

Cas No.:946128-88-7

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5mg
¥987.00
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10mg
¥1,554.00
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25mg
¥3,518.00
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Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

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实验参考方法

Kinase experiment [1]:

Kinase assays

Inhibition of MEK1 was evaluated by a coupled assay with active MEK1 (MEK1 S218E/S222E) and unactive dephosphorylated ERK2 (MAP kinase 2/Erk 2). The phosphorylation of a fluorescent-labeled peptide substrate (FAM-Erktide, IPTTPITTTYFFFK-5FAM-COOH) by ERK2 was quantified by using the IMAP FP Screening Express Kit.

Cell experiment [1]:

Cell lines

HCT116 cell line

Preparation method

This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

Cells were treated with 250 nmol/L CH5126766 in 0.1% DMSO for 2 hours.

Applications

CH5126766 binding could cause MEK to adopt a conformation in which MEK could not be phosphorylated by RAF, resulting in the formation of a stable MEK/RAF complex and inhibition of RAF kinase. Consistent with this mechanism, CH5126766 did not induce MEK phosphorylation.

Animal experiment [1]:

Animal models

HCT116 mouse xenograft model

Dosage form

CH5126766 was dissolved in distilled water containing 5% DMSO and 10% HPCD. Drugs were administrated orally once a day at 1.5 mg/kg.

Application

Daily oral administration of CH5126766 caused significant tumor regression in HCT116 mouse xenograft model.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Ishii N, et al. Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity. Cancer Res. 2013 Jul 1;73(13):4050-60.

产品描述

RO5126766 (CH5126766) is a first-in-class dual inhibitor of Raf/MEK [1].

The RAS/RAF/MEK/ERK signaling pathway is an important signal transduction system and participates in cell differentiation, movement, division and death. Activated Ras activates RAF kinase, which then phosphorylates and activates MEK (MEK1 and MEK2) [1]. The mutations in BRAF, RAS, and NF1 are associated with many human tumors [2].

RO5126766 (CH5126766) is a first-in-class dual Raf/MEK inhibitor. In cell-free kinase assays, CH5126766 effectively inhibited the phosphorylation of MEK1 protein by RAF and the activation of ERK2 protein by MEK1 with IC50 values of 0.0082-0.056 and 0.16 μM, respectively. In NCI-H460 (KRAS Q61H) human lung large cell carcinoma cell line, RO5126766 induced cell-cycle inhibitor p27Kip1 protein expression and caused G1 arrest. In HCT116 KRAS-mutant colorectal cancer cells, RO5126766 CH5126766 completely inhibited the phosphorylation of MEK and ERK [2].

In Japanese patients with advanced solid tumors, RO5126766 exhibited the maximum tolerable dose (MTD) of 2.25 mg/day once daily [1]. In a HCT116 (G13D KRAS) mouse xenograft model, RO5126766 (1.5 mg/kg) inhibited pERK and ERK signaling and exhibited ED50 value of 0.056 mg/kg [2].

References:
[1].  Honda K, Yamamoto N, Nokihara H, et al. Phase I and pharmacokinetic/pharmacodynamic study of RO5126766, a first-in-class dual Raf/MEK inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol, 2013, 72(3): 577-584.
[2].  Ishii N, Harada N, Joseph EW, et al. Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity. Cancer Res, 2013, 73(13): 4050-4060.

Chemical Properties

Cas No. 946128-88-7 SDF
别名 Ro 5126766; CH5126766
Canonical SMILES CC(C1=C(O2)C=C(OC3=NC=CC=N3)C=C1)=C(C2=O)CC4=C(F)C(NS(NC)(=O)=O)=NC=C4
分子式 C21H18FN5O5S 分子量 471.46
溶解度 Soluble in DMSO 储存条件 Store at -20°C
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储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
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溶解性数据

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1 mg 5 mg 10 mg
1 mM 2.1211 mL 10.6054 mL 21.2107 mL
5 mM 0.4242 mL 2.1211 mL 4.2421 mL
10 mM 0.2121 mL 1.0605 mL 2.1211 mL
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