MK-8353 (SCH900353)

製品コードS8701 バッチS870101

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

C37H41N9O3S
分子量 691.84 CAS No. 1184173-73-6
Solubility (25°C)* 体外 DMSO 50 mg/mL (72.27 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）
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
2.5mg/ml
5% DMSO 95% Corn oil
0.41mg/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 MK-8353 (SCH900353) is an orally bioavailable, selective, and potent ERK inhibitor that inhibits activated ERK1 and ERK2 in vitro, with IC50 values of 23.0 nM and 8.8 nM, respectively (IMAP kinase assay), and nonactivated ERK2, with an IC50 of 0.5 nM (MEK1-ERK2-coupled assay).
in vitro

MK-8353 is a potent and selective inhibitor of both active and inactive ERK1 and ERK2 kinases (IC50=20 and 7 nM, respectively). MK-8353 is not a potent inhibitor of human CYPs 1A2, 2C9, 2C19 or 2D6 but inhibits CYP 3A4 (pre-incubation) in vitro and shows inhibition of CYP 3A4 and 2C8 (IC50 = 1.7 & 3.5 μM), which can cause drug-drug interactions when co administered with drugs that are primarily metabolized by CYP 2C8 or 3A4. MK-8353 is a weak inhibitor of hERG current, producing 16% inhibition at 0.6 μM. The IC50 values for inhibiting cell prolifertion are 371, 51, and 23 nM in A2058, HT-29, and Colo-205 cells respectively. In addition to inhibiting the kinase activity of ERK, MK-8353 prevents the phosphorylation of ERK by MEK[1]. MK-8353 demonstrates kinase selectivity over a 227-human kinase panel; no additional kinase in the panel is inhibited by more than 35% at the 0.1 μM concentration, and only 3 kinases (CLK2, FLT4, and Aurora B) are inhibited >50% at the 1.0 μM concentration[2].
in vivo

The in vivo pharmacokinetics and metabolism of MK-8353 are evaluated in male CD1 mice, Sprague Dawley (SD) rats, guinea pigs, beagle dogs, and cynomologus monkeys. With the exception of monkeys, MK-8353 shows moderate clearance after IV administration in all species, with a half-life range of 1.3-2.8 hr and a mean residence time range of 1.5-4.0 hr. Acceptable oral bioavailability is seen in mice, rats and dogs (23-80%) but low oral bioavailability in monkeys (2%). The permeability observed in Caco-2 cells was high (135 nm/sec), suggesting that intestinal absorption and permeability in humans should also be high. The steady-state volume of distribution in mice, dogs and monkeys are in the range of 0.9-3.3 L/kg, while in rats it is 0.1 L/kg. MK-8353 displays anti-tumor efficacy in several BRAF-mutant models[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 A2058 cells
濃度 0, 3, 10, 30, 100, 300 nM
反応時間 24 hours
実験の流れ

A2058 cells (1 × 106 cells per 10-cm dish) were treated with increasing concentrations of MK-8353 (nM) for 24 hours. Whole cell lysates were subjected to immunoblot analysis.
動物実験 動物モデル Female athymic nude mice (inoculated with Colo-205 cancer cells) or SCID mice (inoculated with SK-MEL-28 melanoma cells)
投薬量 30, 45 and 60 mg/kg
投与方法 p.o.

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：

FBXW7 loss of function promotes esophageal squamous cell carcinoma progression via elevating MAP4 and ERK phosphorylation [ J Exp Clin Cancer Res, 2023, 42(1):75] PubMed: 36991467
Connexin 37 sequestering of activated-ERK in the cytoplasm promotes p27-mediated endothelial cell cycle arrest [ Life Sci Alliance, 2023, 6(8)e202201685] PubMed: 37197981
ALV-miRNA-p19-01 Promotes Viral Replication via Targeting Dual Specificity Phosphatase 6 [ Viruses, 2022, 14(4)805] PubMed: 35458535
Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin. [ J Cell Biochem, 2020, 121(1):723-734] PubMed: 31452248
S100A12 promotes inflammation and apoptosis in ischemia/reperfusion injury via ERK signaling in vitro study using PC12 cells [ Pathol Int, 2020, 70(7):403-412] PubMed: 32202379

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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