CC-90003

製品コードS8801 バッチS880101

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C22H21F3N6O2
分子量 458.44 CAS No. 1621999-82-3
Solubility (25°C)* 体外 DMSO 92 mg/mL (200.68 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 CC-90003は、IC50が10～20 nMの不可逆的なERK1/2阻害剤であり、258キナーゼ生化学アッセイにおいて良好なキナーゼ選択性を示します。
in vitro

In biochemical, cellular, and mass spectrometry assays of 347 kinases, CC-90003 was found to strongly inhibit kinase activities of ERK1 and ERK2 with IC50s in the 10 to 20 nmol/L range and had good kinase selectivity. In a 258-kinase biochemical assay panel, significant inhibition of 213 kinases (<50% inhibition), moderate inhibition of 28 kinases (50%–80% inhibition), and >80% inhibition of 17 kinases by this compound were found. In an ActivX cellular kinase screening using A375 BRAF V600E-mutant melanoma cell line, only 5 of 194 kinases (ERK1, ERK2, MKK4, MKK6, and FAK) were inhibited by >80% at 1 mmol/L of this chemical. At the same concentration, no significant inhibition (<14%) was found in a Cerep panel of 40 nonkinase enzymes and receptors. Through our iterative analyses, only 3 kinases, in addition to ERK1/2, were inhibited in cells at biologically relevant concentrations: KDR, FLT3, and PDGFRa. Tumors with BRAF mutations were particularly sensitive to this compound. In many, but not all cases, it had cytotoxic effects in KRAS-mutant PDAC, lung cancer, and colorectal cancer cell lines. It does not significantly inhibit proliferation of normal lung fibroblasts or bronchial epithelial cells.
in vivo

In in vivo studies of an HCT-116 xenograft model, CC-90003 was well tolerated at a range of doses (12.5 mg b.i.d.-100 mg qd), although doses of 50 mpk b.i.d. and 75 mpk b.i.d. group caused mortality by days 6 to 18 of study. Both dosing schedules (qd and b.i.d.) leads to tumor growth inhibition. This compound inhibits tumor growth in vivo of three KRAS-mutant PDX models.

プロトコル(参考用のみ)

細胞アッセイ 細胞株 KRAS-mutant cell lines
濃度 --
反応時間 72 h
実験の流れ

The cells were plated at a density of 3,000 cells/well in 90 mL of growth media on 96-well clear bottom black-well plates and incubated with overnight under standard cell culture growth conditions at 37 C with 5% CO2. The followinging day, one plate for each cell line was used for "Day 0" cell growth control readout, whereas others were treated with 9-point3-fold dilutions of this compound or combination of compounds, and a DMSO control. Each concentration was tested in triplicate. Cell viability was measured 72 hours later.
動物実験 動物モデル Female athymic nude mice inoculated subcutaneously with 5×106 HCT-116 cancer cells
投薬量 100 mg/kg qd and 50 mg/kg qd; 25 mg/kg b.i.d. and 12.5 mg/kg b.i.d.
投与方法 orally

参考

  • https://pubmed.ncbi.nlm.nih.gov/30275173/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

A drug discovery pipeline for MAPK/ERK pathway inhibitors in C. elegans [ Cancer Res Commun, 2024, 10.1158/2767-9764.CRC-24-0221] PubMed: 39212544
Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer [ Cell Death Discov, 2021, 7(1):375] PubMed: 34864826

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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