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SANT-1

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Chemical Structure| 304909-07-7 同义名 : -
CAS号 : 304909-07-7
货号 : A378069
分子式 : C23H27N5
纯度 : 99%+
分子量 : 373.494
MDL号 : MFCD01827306
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(66.94 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
描述 Hedgehog (Hh) signaling normally functions to specify embryonic pattern by directing cellular differentiation and proliferation, whereas aberrant Hh pathway activation is associated with the formation of tumors such as basal cell carcinoma and medulloblastoma. Cellular responses to the secreted Hh polypeptide are mediated by Patched (Ptc) and Smoothened (Smo). SANT-1 is a structurally unrelated Smo antagonist with IC50 value of 20 nM[2]. In vitro, SANT-1 at concentration of 10 μM efficiently inhibited cyclopamine and jervine induced translocation of Smo to the primary cilium in MEFs[1]. SANT-1 inhibited most NSCLC cell lines with IC50 value of 40 μM. Treatment of the EGFR-TKI-resistant cell lines H1975 and A549 with 40 μM SANT-1 for 24h downregulated GLI1 expression and weakened Snail expression, but did not inhibit clonogenic growth. The combination of 40 μM gefitinib and 40 μM SANT-1 synergistically inhibited tumorigenesis and proliferation in EGFR-TKI-resistant NSCLC cell lines H1975 and A549{{Bai XY, Zhang XC, Yang SQ, et al. Blockade of Hedgehog Signaling Synergistically Increases Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancer Cell Lines. PLoS One. 2016;11(3):e0149370|https://www.ncbi.nlm.nih.gov/pubmed/26943330 }}. In vivo, the leukaemia burden was reduced in mice receiving the 1 μM Vorinostat and 2.5 μM SANT-1 treated OCI-AML3 cells[3].
作用机制 SANT-1 binds to a narrow and deep hydrophobic cavity in its 7 transmembrane (TM) domain of Smol[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.68mL

0.54mL

0.27mL

13.39mL

2.68mL

1.34mL

26.77mL

5.35mL

2.68mL
参考文献

[1]Wilson CW, Chen MH, Chuang PT. Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium. PLoS One. 2009;4(4):e5182

[2]Chen JK, Taipale J, Young KE, Maiti T, Beachy PA. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A. 2002;99(22):14071–14076

[3]Hay JF, Lappin K, Liberante F, et al. Integrated analysis of the molecular action of Vorinostat identifies epi-sensitised targets for combination therapy. Oncotarget. 2017;8(40):67891–67903

[4]Fleury A, Hoch L, Martinez MC, et al. Hedgehog associated to microparticles inhibits adipocyte differentiation via a non-canonical pathway. Sci Rep. 2016;6:23479