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UNC2250

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Chemical Structure| 1493694-70-4 同义名 : -
CAS号 : 1493694-70-4
货号 : A202271
分子式 : C24H36N6O2
纯度 : 99%+
分子量 : 440.582
MDL号 : MFCD27992060
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 9 mg/mL(20.43 mM)，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

0.1 M HCL: 10 mg/mL(22.7 mM)，配合低频超声，并调节pH至3
动物实验配方：

5% DMSO+30% PEG 300+water 0.5 mg/mL

生物活性
描述 Mer belongs to the TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases (RTK). This subfamily of RTKs transduce signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Abnormal activation or overexpression of Mer RTK has been implicated in neoplastic progression of many human cancers and has been correlated with poorer prognosis. UNC2250 is a Mer kinase inhibitor which achieved selectivity against the other two members of Tyro3 and Axl. Based on a microfluidic capillary electrophoresis assay, the IC50 of UNC2250 against Mer was 1.7 nM, while the IC50s against Axl and Tyro3 were 270 nM and 100 nM, respectively [2]. UNC2250 inhibited Mer phosphorylation with the IC50 value of 9.8 nM as detected by western blotting[2]. In soft agar colony formation assays, UNC2250 inhibited colony formation of the BT-12 rhabdoid tumor and the NSCLC Colo699 cells[2]. According to another report, UNC2250 inhibited proliferation of the mantle cell lymphoma cell lines Z-138, Mino, and JVM-13 with IC50 values of 3.0 μM, 3.1 μM and 7.7 μM, respectively[3]. In an apoptosis assay, flow cytometry analysis revealed that 4 μM UNC2250 induced apoptosis in Z-138 cells by 45.2% and Mino cells by 44.4% post 12h treatment, and when the time was extended to 24 or 48h, the apoptosis rates induced by 4 μM UNC2250 increased to 76.9 or 98.0% in Z-138 cells and to 81.5 or 98.1% in Mino cells[3]. In an mantle cell lymphoma Z-138 xenograft model established on NOD/SCID mice, UNC2250 was administrated once daily by oral gavage for 10 days. UNC2250 produced significant anti-tumor effects on tumor volume at the doses of 50 and 75 mg/kg. The tumor inhibition rates were 35 and 48%, respectively[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.27mL

0.45mL

0.23mL

11.35mL

2.27mL

1.13mL

22.70mL

4.54mL

2.27mL
参考文献

[1]Zhang W, Zhang D, et al. Pseudo-cyclization through intramolecular hydrogen bond enables discovery of pyridine substituted pyrimidines as new Mer kinase inhibitors. J Med Chem. 2013 Dec 12;56(23):9683-92.

[2]Zhang W, Zhang D, Stashko MA, DeRyckere D, Hunter D, Kireev D, Miley MJ, Cummings C, Lee M, Norris-Drouin J, Stewart WM, Sather S, Zhou Y, Kirkpatrick G, Machius M, Janzen WP, Earp HS, Graham DK, Frye SV, Wang X. Pseudo-cyclization through intramolecular hydrogen bond enables discovery of pyridine substituted pyrimidines as new Mer kinase inhibitors. J Med Chem. 2013 Dec 12;56(23):9683-92. doi: 10.1021/jm401387j. Epub 2013 Nov 20. Erratum in: J Med Chem. 2014 Aug 28;57(16):7141. PMID: 24195762; PMCID: PMC3980660.

[3]Shi C, Li X, Wang X, Ding N, Ping L, Shi Y, Mi L, Lai Y, Song Y, Zhu J. The proto-oncogene Mer tyrosine kinase is a novel therapeutic target in mantle cell lymphoma. J Hematol Oncol. 2018 Mar 20;11(1):43. doi: 10.1186/s13045-018-0584-6. PMID: 29554921; PMCID: PMC5859520.