受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C33H33N9O2 |
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分子量 | 587.67 | CAS No. | 942183-80-4 | |
Solubility (25°C)* | 体外 | DMSO | 28 mg/mL warmed with 50ºC water bath (47.64 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <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 | SCH772984 is a novel, specific inhibitor of ERK1/2 with IC50 values of 4 nM and 1 nM in cell-free assay, respectively, And show robust efficacy in RAS- or BRAF-mutant cancer cells. |
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in vitro | SCH772984 is a novel, selective and ATP competitive inhibitor of ERK1/2. SCH772984 inhibits phosphorylation of the ERK substrate p90 ribosomal S6 kinase (T359/S363 phospho-RSK) in a dose-dependent manner. SCH772984 also inhibits phosphorylation of residues in the activation loop of ERK itself. SCH772984 demonstrates EC50 values <500 nM in approximately 88% and 49% of BRAF-mutant or RAS-mutant tumor lines, respectively. Importantly, SCH772984 effectively inhibited MAPK signaling and cell proliferation in tumor cells resistant to concurrent treatment with BRAF and MEK inhibitors. [1] |
in vivo | SCH772984 induces tumor regressions in xenograft models at tolerated doses. SCH772984 effectively inhibites MAPK signaling and cell proliferation in BRAF or MEK inhibitor resistant models. [1] |
特徴 | Does not directly inhibit MEK1, MEK2, BRAF, or CRAF enzyme activity. |
キナーゼアッセイ | ERK2 IMAP enzymatic assay | |
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SCH772984 is tested in 8 point dilution curves in duplicate against purified ERK2 or ERK1. The enzyme is added to the reaction plate. and incubated with the compound before adding a solution of substrate peptide and ATP. 14μl of diluted enzyme (0.3ng active ERK2 per reaction) is added to each well of a 384-well plate. The plates are gently shaken to mix the reagents and incubated for 45 minutes at room temperature. The reaction is stopped with 60μl of IMAP Binding Solution (1:2200 dilutions of IMAP beads in 1X Binding Buffer). The plates are incubated at room temperature for an additional 0.5 hours to allow complete binding of phosphopeptides to the IMAP beads. Plates are read on the LJL Analyst. | ||
細胞アッセイ | 細胞株 | BRAF-mutant or RAS-mutant tumor lines |
濃度 | ~10 μM | |
反応時間 | 5 days | |
実験の流れ | Cell proliferation experiments are performed in a 96-well format (six replicates), and cells are plated at 4,000/well density. At 24 h after cell seeding, cells are treated with DMSO or 9 point IC50 dilution (0.001-10 μM) at 1% DMSO final for all concentrations. Viability is assayed on 5 days after dosing using ViaLight luminescence kit following the manufacturer’s recommendations. For cell line panel viability assay, cells are treated with SCH772984 for 4 days and assayed by CellTiterGlo luminescent cell viability assay. |
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動物実験 | 動物モデル | Nude mice |
投薬量 | 12.5 mg/kg, 25 mg/kg, 50 mg/kg | |
投与方法 | i.p. |
Data from [Data independently produced by Leuk Lymphoma, 2014, 1, 8]
, , Biochem Biophys Res Commun, 2017, 485(4):775-781
Data from [Data independently produced by , , Nature, 2016, 534(7609):647-51]
The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34 [ Nat Commun, 2024, 15(1):383] | PubMed: 38195627 |
PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer [ Cell Rep Med, 2024, 5(2):101420] | PubMed: 38382468 |
The DNA-dependent protein kinase catalytic subunit exacerbates endotoxemia-induced myocardial microvascular injury by disrupting the MOTS-c/JNK pathway and inducing profilin-mediated lamellipodia degradation [ Theranostics, 2024, 14(4):1561-1582] | PubMed: 38389837 |
Tubuloid differentiation to model the human distal nephron and collecting duct in health and disease [ Cell Rep, 2024, 43(1):113614] | PubMed: 38159278 |
Combined RAF and MEK Inhibition to Treat Activated Non-V600 BRAF-Altered Advanced Cancers [ Oncologist, 2024, 29(1):15-24] | PubMed: 37616543 |
Cell-free ascites from ovarian cancer patients induces Warburg metabolism and cell proliferation through TGFβ-ERK signaling [ Geroscience, 2024, 10.1007/s11357-023-01056-1] | PubMed: 38196068 |
Hepatitis C virus modified sE2F442NYT as an antigen in candidate vaccine facilitates human immune cell activation [ J Virol, 2024, 98(1):e0180923] | PubMed: 38084956 |
Testosterone reduces hippocampal synaptic damage in an androgen receptor-independent manner [ J Endocrinol, 2024, 260(2)e230114] | PubMed: 37991884 |
p90RSK pathway inhibition synergizes with cisplatin in TMEM16A overexpressing head and neck cancer [ BMC Cancer, 2024, 24(1):233] | PubMed: 38373988 |
Hyperglycemia activates FGFR1 via TLR4/c-Src pathway to induce inflammatory cardiomyopathy in diabetes [ Acta Pharmaceutica Sinica B, 2024, 10.1016/j.apsb.2024.01.013] | PubMed: none |
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。