受注:045-509-1970 |
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Synonyms | G-868 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C16H14FIN4O3 |
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分子量 | 456.21 | CAS No. | 1168091-68-6 | ||||
Solubility (25°C)* | 体外 | DMSO (warmed with 50ºC water bath) | 91 mg/mL (199.46 mM) | ||||
Ethanol (warmed with 50ºC water bath) | 6 mg/mL (13.15 mM) | ||||||
Water | ˂1 mg/mL | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | GDC-0623 (G-868) is a potent and ATP-uncompetitive MEK1 inhibitor with Ki of 0.13 nM. Phase 1. |
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in vitro | In a panel of mutant cancer cell lines, GDC-0623 inhibits cellular proliferation with EC50 of 4 nM, 53 nM, 11 nM, 18 nM and 94 nM for A375 (BRAFV600E), HCT116 (KRASG13D), COLO 205 (V600E), HT-29 (V600E), and HCT116 (G13D) cells, respectively. [1] In isogenic KRAS HCT116 and mutant KRAS SW620 colon cells, GDC-0623 upregulates BIM via its loss of phosphorylation at Ser69. GDC-0623 plus ABT-263 induces a synergistic cell apoptosis. [2] |
in vivo | In vivo, GDC-0623 (40 mg/kg, p.o.) causes potent tumor growth inhibition (TGI) in mouse MiaPaCa-2 (120%), A375 (102%) and HCT116 (115%) xenografts. [1] |
キナーゼアッセイ | In vitro Kinase assays | |
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0.14 μM of purified inactive recombinant MEK-1 (Upstate) protein is preincubated with inhibitors in 15 μL of kinase buffer including (20 mM MOPS pH7.2, 25 mM beta glycerol phosphate, 5 mM EGTA, 1 mM sodium orthovanadate, 1 mM DTT, 100 μM ATP, 15 mM MgCl2). After incubating 10 minutes at 30°C, 1 ng of BRAF, CRAF or BRAF V600E combined with 0.5 μg of inactive recombinant ERK2 is added to the reaction in total volume of 20 μL. After incubating 30 minutes at 30°C the reaction is stopped by adding Laemmle sample buffer. Enzyme activity is measured by determining level of phosphor-MEK by SDS-PAGE. Immunoreactive proteins are visualized with SuperSignal West Pico Chemiluminescent Substrate. | ||
細胞アッセイ | 細胞株 | A375 (BRAFV600E), HCT116 (KRASG13D), COLO 205 (V600E), HT-29 (V600E), and HCT116 (G13D) cells |
濃度 | ||
反応時間 | 24 hours | |
実験の流れ | Cell lines are maintained at 37癈 and 5% CO2 in DMEM with 10% fetal bovine serum and 4 mM L-glutamine. The cell lines are verified by high-throughput SNP genotyping using Illumina Golden Gate multiplexed assays and SNP profiles are compared to the Sanger database to confirm ancestry. Viability following compound treatment is assessed via ATP content using the CellTiter-Glo Luminescent Assay. | |
動物実験 | 動物モデル | Mice bearing MiaPaCa-2, A375 and HCT116 xenografts |
投薬量 | 40 mg/kg daily | |
投与方法 | p.o. |
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Data from [Data independently produced by , , Mol Cell Proteomics, 2017, 16(2):265-277]
High In Vitro and In Vivo Activity of BI-847325, a Dual MEK/Aurora Kinase Inhibitor, in Human Solid and Hematologic Cancer Models [ Cancer Res Commun, 2023, 3(10):2170-2181] | PubMed: 37830744 |
Neuronal differentiation drives the antitumor activity of mitogen-activated protein kinase kinase (MEK) inhibition in glioblastoma [ Neurooncol Adv, 2023, 5(1):vdad132] | PubMed: 38130900 |
High In Vitro and In Vivo Activity of BI-847325, a Dual MEK/Aurora Kinase Inhibitor, in Human Solid and Hematologic Cancer Models [ Cancer Res Commun, 2023, 3(10):2170-2181] | PubMed: 37830744 |
DAMPs Released From Injured Renal Tubular Epithelial Cells Activate Innate Immune Signals in Healthy Renal Tubular Epithelial Cells [ Transplantation, 2022, 106-8:1589-1599] | PubMed: 34954736 |
Efficacy of Targeted Radionuclide Therapy Using [131I]ICF01012 in 3D Pigmented BRAF- and NRAS-Mutant Melanoma Models and In Vivo NRAS-Mutant Melanoma [ Cancers (Basel), 2021, 13(6)1421] | PubMed: 33804655 |
MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways [ Int J Endocrinol, 2021, 2021:5720145] | PubMed: 34976051 |
CAGE-prox: A Unified Approach for Time-Resolved Protein Activation in Living Systems [ Curr Protoc, 2021, 1(6):e180] | PubMed: 34165886 |
Time-resolved protein activation by proximal decaging in living systems [Wang J, et al. Nature, 2019, 569(7757):509-513] | PubMed: 31068699 |
Genetic Heterogeneity of BRAF Fusion Kinases in Melanoma Affects Drug Responses. [ Cell Rep, 2019, 29(3):573-588] | PubMed: 31618628 |
Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer [ Oncogenesis, 2019, 8(2):11] | PubMed: 30741938 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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