产品说明书

Vadimezan

Print
Chemical Structure| 117570-53-3 同义名 : 伐地美生 ;DMXAA;ASA-404;AS1404;5,6-Dimethylxanthenone-4-acetic Acid;NSC 640488
CAS号 : 117570-53-3
货号 : A140665
分子式 : C17H14O4
纯度 : 98%
分子量 : 282.291
MDL号 : MFCD00870555
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 6 mg/mL(21.25 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：

IP 2% DMSO+2% Tween80+30% PEG300+water 0.2 mg/mL clear

PO 0.5% CMC-Na 31 mg/mL suspension

生物活性
靶点

  • VDA

    DT-diaphorase, Ki:20 μM
描述 DMXAA is a competitive inhibitor of DT-diaphorase with an IC50 value of 62.5μM and a Ki value of 20μM. DMXAA blocked DT-diaphorase activity in DLD-1 cells with an IC50 value of 49.6μM. It led to approximate 25% inhibition of cytochrome b5 reductase, although the inhibition plateau was between 250μM and 2 mM[1]. DMXAA also showed potent inhibitory effect on vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, as well as other protein kinases including homeodomain-interacting protein kinase 2, casein kinase 2, Haspin, Aurora kinases, PIM kinases, c-FMS, and tropomyosin-receptor kinases. The IC50 values of DMXAA against VEGFR1 and VEGFR2 were 119 and 11μM, respectively. DMXAA at 25μM showed partial anti-angiogenic effect in an embryonic zebrafish model. DMXAA at the concentration of 30μM significantly reduce the VEGF-induced activation of extracellular-signal-regulated kinase in human umbilical vein endothelial cells[2]. In female Wistar rats, a single dose of DMXAA (300mg/kg, i.p.) significantly delayed the growth of NMU-induced primary mammary tumors as compared to vehicle-treated group[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HECPP cells 10 ug/mL Function assay Activation of NF-kappaB in HECPP cells at 10 ug/mL 17616114
human BJ cells Cytotoxic assay 24 h Cytotoxicity against human BJ cells after 24 hrs by MTT assay, CC50=48.9 μM 24518295
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
NCT01031212 Tumors Phase 1 Withdrawn(The investigator has... 展开 >> left the institution (UCSF) prior to study start-up) 收起 << June 2013 United States, California ... 展开 >> UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California, United States, 94115 收起 <<
NCT00662597 Non-Small Cell Lung Cancer Phase 3 Terminated - -
NCT01057342 Lung Cancer Phase 2 Completed - Switzerland ... 展开 >> Saint Claraspital AG Basel, Switzerland, CH-4016 Universitaetsspital-Basel Basel, Switzerland, CH-4031 Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni Bellinzona, Switzerland, CH-6500 Inselspital Bern Bern, Switzerland, CH-3010 Spitalzentrum Biel Biel, Switzerland, CH-2501 Centre Hospitalier Universitaire Vaudois Lausanne, Switzerland, CH-1011 Kantonsspital Olten Olten, Switzerland, CH-4600 Onkologie Schaffhausen Schaffhausen, Switzerland, CH-8200 Kantonsspital - St. Gallen St. Gallen, Switzerland, CH-9007 Regionalspital Thun, Switzerland, 3600 Kantonsspital Winterthur Winterthur, Switzerland, CH-8400 Klinik Hirslanden Zurich, Switzerland, CH-8032 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.54mL

0.71mL

0.35mL

17.71mL

3.54mL

1.77mL

35.42mL

7.08mL

3.54mL
参考文献

[1]Phillips RM. Inhibition of DT-diaphorase (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) by 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and flavone-8-acetic acid (FAA): implications for bioreductive drug development. Biochem Pharmacol. 1999 Jul 15;58(2):303-10.

[2]Buchanan CM, Shih JH, Astin JW, Rewcastle GW, Flanagan JU, Crosier PS, Shepherd PR. DMXAA (Vadimezan, ASA404) is a multi-kinase inhibitor targeting VEGFR2 in particular. Clin Sci (Lond). 2012 May 1;122(10):449-57.

[3]Liu JJ, Ching LM, Goldthorpe M, Sutherland R, Baguley BC, Kirker JA, McKeage MJ. Antitumour action of 5,6-dimethylxanthenone-4-acetic acid in rats bearing chemically induced primary mammary tumours. Cancer Chemother Pharmacol. 2007 Apr;59(5):661-9.

[4]Zhao L, Kestell P, et al. Oral activity and pharmacokinetics of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in mice. Cancer Chemother Pharmacol. 2002 Jan;49(1):20-6.