受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
Synonyms | AR-00341677 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
||||
化学式 | C19H18N4O2 |
||||||
分子量 | 334.37 | CAS No. | 905281-76-7 | ||||
Solubility (25°C)* | 体外 | DMSO (warmed with 50ºC water bath) | 66 mg/mL (197.38 mM) | ||||
Ethanol | 7 mg/mL (20.93 mM) | ||||||
Water | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
|
||||||
* <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-0879 (AR-00341677) is a novel, potent, and selective B-Raf inhibitor with IC50 of 0.13 nM in A375 and Colo205 cells with activity against c-Raf as well; no inhibition known to other protein kinases. |
---|---|
in vitro | GDC-0879 also inhibits cellular pERK with IC50 of 63 nM. GDC-0879 shows comparable potency in A375 melanoma and Colo205 colorectal carcinoma cell lines, both of which are B-RafV600E mutant, with IC50 of 59 nM and 29 nM for pMEK1 inhibition respectively. GDC-0879 potently inhibits B-RafV600E in Malme3M cells with IC50 of 0.75 μM. GDC-0879 also shows EC50 values < 0.5 μM in many tumor cells (A375, 624, SK-MEL-28, Malme3M, C32, 928, 888, G-361, Colo205, Colo206, SW1417, CL34, and Colo201). [1] |
in vivo | In GDC-0879 treated mice, both cell line- and patient-derived BRAFV600E tumors exhibit stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared to mutant KRAS-expressing tumors. Although there is involvement of activated RAF signaling in RAS-induced tumorigenesis, decreased time to progression is observed for some KRAS-mutant tumors following GDC-0879 administration. Whereas GDC-0879-mediated efficacy is associated strictly with B-RafV600E status, MEK inhibition also attenuates proliferation and tumor growth of cell lines expressing wild-type BRAF (81% KRAS mutant, 38% KRAS wild type). The responsiveness of B-RafV600E melanoma cells to GDC-0879 could be dramatically altered by pharmacologic and genetic modulation of PI3K pathway activity. [2] |
動物実験 | 動物モデル | Female nu/nu mice |
---|---|---|
投薬量 | 100 mg/kg | |
投与方法 | Oral gavage |
|
Data from [J Natl Cancer Inst, 2012, 104(21), 1673-9]
Data from [J Natl Cancer Inst, 2012, 104(21), 1673-9]
Data from [Proc Natl Acad Sci USA, 2011, 108, 6067-6072]
BRAFΔβ3-αC in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability [ Sci Adv, 2023, 9(35):eade7486] | PubMed: 37656784 |
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] | PubMed: 35868306 |
Inhibition of IκB Kinase Is a Potential Therapeutic Strategy to Circumvent Resistance to Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2022, 14(21)5215] | PubMed: 36358633 |
AKT1/FOXP3 axis-mediated expression of CerS6 promotes p53 mutant pancreatic tumorigenesis [ Cancer Lett, 2021, S0304-3835(21)00309-8] | PubMed: 34343636 |
Dual Inhibition of AKT and MEK Pathways Potentiates the Anti-Cancer Effect of Gefitinib in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2021, 13(6)1205] | PubMed: 33801977 |
A Live-Cell Screen for Altered Erk Dynamics Reveals Principles of Proliferative Control. [ Cell Syst, 2020, 10(3):240-253] | PubMed: 32191874 |
RAF kinases are stabilized and required for dendritic cell differentiation and function. [ Cell Death Differ, 2019, 10.1038/s41418-019-0416-4] | PubMed: 31541179 |
An Anticancer Drug Cocktail of Three Kinase Inhibitors Improved Response to a Dendritic Cell-Based Cancer Vaccine [ Cancer Immunol Res, 2019, 7(9):1523-1534] | PubMed: 31266784 |
mTOR inhibitor everolimus reduces invasiveness of melanoma cells. [ Hum Cell, 2019, 10.1007/s13577-019-00270-4] | PubMed: 31586300 |
Mitochondrial metabolic reprograming via BRAF inhibition ameliorates senescence. [ Exp Gerontol, 2019, 126:110691] | PubMed: 31421186 |
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。