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
* <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 is an irreversible inhibitor of ERK1/2 with IC50s in the 10-20 nM range and shows good kinase selectivity in a 258-kinase biochemical assay.
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 CC-90003 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 CC-90003. 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 CC-90003. In many, but not all cases, CC-90003 had cytotoxic effects in KRAS-mutant PDAC, lung cancer, and colorectal cancer cell lines. CC-90003 does not significantly inhibit proliferation of normal lung fibroblasts or bronchial epithelial cells[1].
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. CC-90003 inhibits tumor growth in vivo of three KRAS-mutant PDX models[1].

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 one 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

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：

Targeting ERK induced cell death and p53/ROS-dependent protective autophagy in colorectal cancer [ Cell Death Discov, 2021, 7(1):375] PubMed: 34864826

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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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