ON123300

製品コードS8161 バッチS816102

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H27N7O
分子量 429.52 CAS No. 1357470-29-1
Solubility (25°C)* 体外 DMSO 29 mg/mL (67.51 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 ON123300 is a potent and multi-targeted kinase inhibitor with IC50 of 3.9 nM, 5 nM, 26 nM, 26 nM, 9.2 nM and 11nM for CDK4, Ark5/NUAK1, PDGFRβ, FGFR1, RET (c-RET), and Fyn, respectively.
in vitro

ON123300 inhibits U87 glioma cell proliferation with an IC50 3.4±0.1 μmol/L and reduces phosphorylation of Akt, yet it also unexpectedly induces Erk activation, both in a dose- and time-dependent manner that subsequently is attributed to relieving Akt mediated C-Raf S259 inactivation and activating a p70S6K-initiated PI3K-negative feedback loop[1]. ON123300 also inhibits CDK4/6 and PI3K-δ and exhibits potent activity against mantle cell lymphomas (MCLs). ON123300 is a potent inhibitor of CDK4, with an IC50 of 3.8 nM, with little inhibitory activity against CDKs 1,2,5 and 8. MCL cell lines treated with ON123300 accumulate in the G1 phase at lower concentrations (0.1-1.0μM), at higher concentrations of the compound, a large proportion of the cells progress through the S and G2/M phases of the cell cycle and eventually accumulate in the sub-G1 phase, suggesting an induction of apoptosis. ON123300 also inhibits the phosphorylation of pRb and p130 in a dose-dependent manner. ON123300 treatment results in inhibition of FOXO1 phosphorylation, a target of mTOR[3].
in vivo

In a preclinical brain tumor model (U87MG), ON123300 shows high brain and brain tumor accumulation. Consistent with the in vitro studies, single agent ON123300 causes a dose-dependent suppression of phosphorylation of Akt as well as activation of Erk in brain tumors[1]. ON123300 is highly bound (99.4%) to plasma proteins in mice and rapidly penetrates into brain. It has proficient BBB penetration and accumulates in normal brain[2]. The pharmacokinetic profiles of plasma ON123300 concentration are multiexponential and overall declines fairly rapidly with terminal elimination half-lives of 1.5 hours[1]. Mouse xenograft assays show a strong inhibition of MCL tumor growth in ON123300-treated animals. Safety studies in mice suggest that ON123300 is orally bio-available and is minimally toxic when administered orally or intraperitoneally[3].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 U87 glioma cells
濃度 --
反応時間 72 h
実験の流れ

The cytotoxicity of ON123300 is determined using a colorimetric sulforhodamine B (SRB)-based assay. Suspensions of glioma cells (100 mL containing 2×103 cells) are seeded in 96-well plates and allowed to attach to the surface by overnight incubation. The cells are then treated with increasing concentrations of ON123300 for 72 hour. At the end of the treatment, cells are fixed with 10% (v/v) trichloroacetic acid (TCA) and stained with 0.4% SRB. The optical densities are measured at a wavelength of 570 nm. 
動物実験 動物モデル NIH Swiss nude mice
投薬量 5 and 25 mg/kg
投与方法 i.v.

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：

Activation of salt Inducible Kinases, IRE1 and PERK leads to Sec bodies formation in Drosophila S2 cells [ J Cell Sci, 2021, jcs.258685] PubMed: 34350957
Synergistic Anti Leukemia Effect of a Novel Hsp90 and a Pan Cyclin Dependent Kinase Inhibitors. [ Molecules, 2020, 8;25(9) pii: E2220] PubMed: 32397330

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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