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Dovitinib lactate

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Chemical Structure| 692737-80-7 同义名 : TKI-258 lactate;CHIR-258 lactate
CAS号 : 692737-80-7
货号 : A445850
分子式 : C24H27FN6O4
纯度 : 99%+
分子量 : 482.507
MDL号 : MFCD16038905
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: 25 mg/mL(51.81 mM)，配合低频超声助溶，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
描述 Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) signaling network play essential roles to promote angiogenesis and tumor growth by binding to tyrosine kinase. Dovitinib (TKI258) is a small-molecule tyrosine kinase inhibitor targeting multiple RTKs, such as FGFRs. Dovitinib decreased the cell numbers in a dose-dependent manner in HCC1937 cells (IC50 = 13.8 μM), MCF-7 cells (IC50 = 12.7 μM), MDA-MB-231 cells (IC50 = 11.9 μM), MDA-MB-453 cells (IC50 = 9.7 μM), MDA-MB-468 cells (IC50 = 10.1 μM), and SK-BR-3 cells (IC50 = 11.7 μM). Dovitinib (0, 10, 15 μM; 24 h) induced the autophagy of various breast cancer cells through inhibiting STAT3/Mcl-1 axis in a dose-dependent manner. Treatment with 15 μM dovitinib induced about 15%, 40%, 25%, and 17% cell apoptosis at 24 h for MCF-7, MDA-MB-231, MDA-MB-468, and SK-BR-3 cells, respectively[3]. In mice bearing subcutaneous AN3CA, MFE296, SNGM, or HEC1A tumor xenografts, dovitinib (daily oral doses of 30 or 50 mg/kg) significantly delayed the growth of FGFR2-mutated endometrial cancer xenograft tumors. Of note, complete tumor regressions were observed in the majority of tumors at a dovitinib dose of 50 mg/kg in the SNGM xenograft model[4].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01678105 Recurrent Adenoid Cystic Carci... 展开 >>noma of the Salivary Glands Metastatic Adenoid Cystic Carcinoma of the Salivary Glands Salivary Gland Cancers ACC 收起 << Phase 2 Completed - Canada, Ontario ... 展开 >> Tom Baker Cancer Centre Calgary, Ontario, Canada, T2N 4N2 Juravinski Cancer Centre Hamilton, Ontario, Canada, L8V 5C2 London Health Sciences Centre London, Ontario, Canada, N6A 4L6 Ottawa Hospital Regional Cancer Centre Ottawa, Ontario, Canada, K1H 8L6 收起 <<
NCT01223027 Metastatic Renal Cell Carcinom... 展开 >>a 收起 << Phase 3 Completed - -
NCT01496534 Solid Tumors ... 展开 >>Bladder Cancer 收起 << Phase 1 Terminated(toxicity of combina... 展开 >>tion of medications) 收起 << - United States, New York ... 展开 >> Icahn School of Medicine at Mount Sinai New York, New York, United States, 10029 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.07mL

0.41mL

0.21mL

10.36mL

2.07mL

1.04mL

20.73mL

4.15mL

2.07mL
参考文献

[1]Huynh H, Chow PK, et al. Dovitinib demonstrates antitumor and antimetastatic activities in xenograft models of hepatocellular carcinoma. J Hepatol. 2012 Mar;56(3):595-601.

[2]Trudel S, Li ZH, et al. CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood. 2005 Apr 1;105(7):2941-8.

[3]Chiu YH, et al. Dovitinib Triggers Apoptosis and Autophagic Cell Death by Targeting SHP-1/p-STAT3 Signaling in Human Breast Cancers. J Oncol. 2019 Aug 14;2019:2024648.

[4]Konecny GE, et al. Activity of the fibroblast growth factor receptor inhibitors dovitinib (TKI258) and NVP-BGJ398 in human endometrial cancer cells. Mol Cancer Ther. 2013 May;12(5):632-42.