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Chemical Structure| 1357470-29-1 同义名 : ON 123300
CAS号 : 1357470-29-1
货号 : A414519
分子式 : C24H27N7O
纯度 : 99%+
分子量 : 429.517
MDL号 : MFCD28411414
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 16 mg/mL(37.25 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • FGFR1

    FGFR1, IC50:26 nM

  • CDK4

    CDK4/CyclinD1, IC50:3.87 nM

  • CDK6

    CDK6/CyclinD1, IC50:9.82 nM
描述 The cyclin-dependent kinases (CDKs) have a central role in coordinating the eukaryotic cell division cycle, and also serve to integrate diverse growth-regulatory signals[5]. ON123300 is an effective multi-target kinase inhibitor against CDK4 and ARK5, two kinases intimately associated with growth, survival and metastasis of human tumor cells with IC50s of 3.9 nM, 5 nM, respectively. Z138C cells treated with ON123300 for 24 hours accumulated in the G1 phase at lower concentrations (0.1–1.0 µM), at higher concentrations of this compound, a large proportion of the cells progressed through the S and G2/M phases of the cell cycle and eventually accumulated in the sub-G1 phase, suggesting an induction of apoptosis. Granta 519 and Z138C cells were treated with increasing concentrations of ON123300 for 24 hours. ON123300 repressed the phosphorylation of pRb and p130 in a dose-dependent manner suggesting that ON123300 inactivated the Rb (Retinoblastoma family of proteins) pathway due to the inhibition of CDK4 in the two MCL (mantle cell lymphoma) cell lines. Mice with tumor xenografts were randomly assigned into 2 treatment groups and treated daily with either water (vehicle) or ON123300 (100mg/kg) on a daily basis. Treatment with ON123300 significantly inhibited (p<0.05) tumor growth over a 2-week period, suggesting that this compound is a potent inhibitor of MCL proliferation in vivo[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.33mL

0.47mL

0.23mL

11.64mL

2.33mL

1.16mL

23.28mL

4.66mL

2.33mL
参考文献

[1]Zhang X, Lv H, et al. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol Cancer Ther. 2014 May;13(5):1105-16.

[2]Lv H, Zhang X, et al. Integrated pharmacokinetic-driven approach to screen candidate anticancer drugs for brain tumor chemotherapy. AAPS J. 2013 Jan;15(1):250-7.

[3]Mudunuru J, Ren C, et al. Effect of Gender on the Pharmacokinetics of ON 123300, A Dual Inhibitor of ARK5 and CDK4/6 for the Treatment of Cancer, in Rats. Eur J Drug Metab Pharmacokinet. 2019 Aug;44(4):531-538.

[4]ON 123300, an Orally Administered Novel CDK4/6 + ARK5 Inhibitor, Exhibits Potent Antitumor Activity In Vivo: Comparative Studies with Palbociclib

[5]Pavletich NP. Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J Mol Biol. 1999 Apr 16;287(5):821-8. doi: 10.1006/jmbi.1999.2640. PMID: 10222191.

[6]Divakar SK, Ramana Reddy MV, Cosenza SC, Baker SJ, Perumal D, Antonelli AC, Brody J, Akula B, Parekh S, Reddy EP. Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas. Leukemia. 2016 Jan;30(1):86-93. doi: 10.1038/leu.2015.185. Epub 2015 Jul 15. PMID: 26174628; PMCID: PMC4703501.