MCE 的所有產品僅用作科學研究或藥證申報，我們不為任何個人用途提供產品和服務。

Avutometinib

CAS No. : 946128-88-7

產品活性：Avutometinib (Ro 5126766) is a first-in-class dual MEK/RAF inhibitor that allosterically inhibits BRAF^V600E, CRAF, MEK, and BRAF (IC₅₀: 8.2, 56, 160 nM, and 190 nM, respectively).

研究領域：MAPK/ERK Pathway

作用靶點：MEK  |  Raf

In Vitro: 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^V600E (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 mevalonate pathway affects the sensitivity to MEK inhibitors, human breast cancer MDA-MB-231 cells harboring KRAS and BRAF mutations are treated Avutometinib, with or without statins, which inhibits HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway. The combined treatment of Avutometinib with XU 62-320 demonstrates more significant reduction in cell growth in a dose-dependent manner than the single treatment of Avutometinib. The marked combined effects of Avutometinib at 40 nM and XU 62-320 at 0.3 μM is also confirmed on the suppression of the colony formation of the cells.

In Vivo: 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 ED₅₀ for Ro 5126766 of 0.03 to 0.23 mg/kg and an ED₉₀ 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 ED₅₀ for Avutometinib and PD0325901 are 0.056 and 0.80 mg/kg, respectively. Therefore, the doses used for this experiment are 26.8- and 31.3-fold higher doses than the 50% effective doses, respectively. Daily oral administration of either drug causes significant tumor regression of each these tumors. However, whereas inhibition of tumor growth is maintained for the entire 28-day treatment period in Avutometinib-treated mice, tumor models receiving PD0325901 become refractory after 10 days of treatment.

相關產品：Clinical Compound Library Plus  |  Bioactive Compound Library Plus  |  Immunology/Inflammation Compound Library  |  Kinase Inhibitor Library  |  MAPK Compound Library  |  Anti-Cancer Compound Library  |  Clinical Compound Library  |  Reprogramming Compound Library  |  Oxygen Sensing Compound Library  |  Ferroptosis Compound Library  |  Glutamine Metabolism Compound Library  |  Anti-Breast Cancer Compound Library  |  Anti-Lung Cancer Compound Library  |  Anti-Pancreatic Cancer Compound Library  |  Anti-Obesity Compound Library  |  Angiogenesis-Related Compound Library  |  Anti-Liver Cancer Compound Library   |  Anti-Colorectal Cancer Compound Library   |  Heterocyclic Compound Library  |  Pain-Related Compound Library  |  Membrane Protein-targeted Compound Library  |  Membrane Receptor-targeted Compound Library  |  B-Raf IN 2  |  Sorafenib-d₄  |  AZ 628  |  B-Raf IN 7  |  Cobimetinib racemate  |  Antitumor agent-60  |  Trametinib (DMSO solvate)  |  Sorafenib Tosylate  |  Dabrafenib Mesylate  |  SB-682330A  |  PD184161  |  Belvarafenib TFA  |  GW284543 hydrochloride  |  L-779450  |  trans-Zeatin-d₅  |  BI-847325  |  Hypothemycin  |  B-Raf IN 9  |  Debromohymenialdisine  |  Raf inhibitor 1  |  TBAP-001  |  RRD-251  |  BI-882370  |  Encorafenib-¹³C,d₃  |  PLX-4720  |  RGB-286638  |  Binimetinib  |  TAK-632  |  Norartocarpetin

熱門產品線：重組蛋白  |  化合物庫  |  天然產物  |  熒光染料  |  PROTAC  |  同位素標記物  |  寡核苷酸  |  抗體  |  點擊化學

Trending products：Recombinant Proteins  |  Bioactive Screening Libraries  |  Natural Products  |  Fluorescent Dye  |  PROTAC  |  Isotope-Labeled Compounds  |  Oligonucleotides  |  Antibodies  |  Click Chemistry

品牌介紹:
•   MCE (MedChemExpress) 擁有200 多種*僅有化合物庫，我們致力于為*科研客戶提供前沿的高品質小分子活性化合物；
•   50,000 多種高選擇性抑制劑、激動劑涉及各熱門信號通路及疾病領；
•   產品種類涵蓋各種重組蛋白，多肽，常用試劑盒 ，更有 PROTAC、ADC 等特色產品，廣泛應用于新藥研發、生命科學等科研項目；
•   提供虛擬篩選，離子通道篩選，代謝組學分析檢測分析，藥物篩選等專業技術服務；
•   設有專業的實驗中心和嚴格的質控、驗證體系；
•   提供 LC/MS、NMR、HPLC、手性分析、元素分析等各項質檢報告，確保產品的高純度、高品質；
•   產品的生物活性多經各國客戶實驗驗證；
•   Nature, Cell, Science 等多種頂級期刊及制藥 Patent 收錄了MCE客戶的科研成果；
•   專業團隊跟蹤新的制藥及生命科學研究進展，為您提供*新的活性化合物；
•   與世界各大制藥公司及*科研機構建立了長期的合作。