艾美捷Thapsigargin毒胡萝卜素化学性质&体外研究

Thapsigargin 是一种有效的、非竞争性的 the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) 的抑制剂，对carbachol诱导的[Ca2+]i瞬变在存不存在KCl预刺激条件下的IC50值分别为0.353 nM和0.448 nM。Thapsigargin 可诱导细胞凋亡。Thapsigargin 提取自植物Thapsia garganica。

艾美捷Thapsigargin技术信息：

正式名称：

(3S,3aS,4R,6R,7S,8R)-6-acetoxy-4-(butyryloxy)-3,3a-dihydroxy-3,6,9-trimethyl-8-(((Z)-2-methylbut-2-enoyl)oxy)-2-oxo-2,3,3a,4,5,6,6a,7,8,9b-decahydro-1H-cyclopenta[e]azulen-7-yl octanoate

CAS编号：67526-95-8

分子式：C34H50O12

公式重量：650.8

纯度：≥97%

配方：结晶状固体

溶解度：

DMF: 30 mg/ml

DMSO：30毫克/毫升

乙醇：30毫克/毫升

乙醇：PBS（pH7.2）（1：2）。0.3 mg/ml

运输和存储信息：

储存：-20°C

运输：美国大陆的室温；其他地方可能有所不同

稳定性：≥ 4年

艾美捷Thapsigargin体外研究：

Thapsigargin以时间和剂量依赖的方式阻止MH7A人类类风湿性关节炎滑膜细胞的增殖。

Thapsigargin损害mTOR活性并导致MH7A细胞中细胞周期蛋白D1的表达。

Thapsigargin抑制Ca2+进入人类中性粒细胞。

Thapsigargin在有（IC50=0.353 nM）或没有（IC50=0.448 nM）KCl-prestimulation的情况下，都能抑制卡巴乔诱发的[Ca2+]i-transients，但在没有KCl-prestimulation的情况下，观察到另外一个小的成分，其敏感性要低很多（IC50=4814 nM）。相比之下，lv化物诱发的[Ca2+]i-transients只显示了一个成分，在没有（IC50=3343 nM）和有（IC50=6858 nM）卡巴胆刺激的情况下，对Thapsigargin的敏感性都非常低。

Thapsigargin还通过SOCE的Ca2+流入使p38 MAPK磷酸化，导致TNF-α诱导的NF-κB磷酸化受到抑制。

艾美捷Thapsigargin文献参考：

1. Sabala, P., Czarny, M., Woronczak, J.P., et al. Thapsigargin: Potent inhibitor of Ca2+ transport ATP-ases of endoplasmic and sarcoplasmic reticulum. Acta Biochim. Pol. 40(3), 309-319 (1993).

2. Treiman, M., Caspersen, C., and Christensen, S.B. A tool coming of age: Thapsigargin as an inhibitor of sarco-endoplasmic reticulum Ca2+-ATPases. Trends Pharmacol. Sci. 19(4), 131-135 (1998).

3. Ali, H., Christensen, S.B., Foreman, J.C., et al. The ability of thapsigargin and thapsigargicin to activate cells involved in the inflammatory response. Br. J. Pharmacol. 85(3), 705-712 (1985).

4. Jackson, T.R., Patterson, S.I., Thastrup, O., et al. A novel tumour promoter, thapsigargin, transiently increases cytoplasmic free Ca2+ without generation of inositol phosphates in NG115-401L neuronal cells. Biochem. J. 253(1), 81-86 (1988).

5. Christensen, S.B., Skytte, D.M., Deanmeade, S.R., et al. A Trojan horse in drug development: Targeting of thapsigargins towards prostate cancer cells. Anticancer Agents Med. Chem. 9(3), 276-294 (2009).

6. Ghantous, A., Gali-Muhtasib, H., Saliba, N.A., et al. What made sesquiterpene lactones reach cancer clinical trials? Drug Discov. Today 15(15-16), 668-678 (2010).

艾美捷Thapsigargin文献引用：

1.Nagakannan, P., Islam, M.I., Conrad, M., et al. Cathepsin B is an excutioner of ferroptosis. Biochim. Biophys. Acta Mol. Cell Res. 1868(3), 118928 (2021).

2.Merhi, A., Delrée, P., and Marini, A. The metabolic waste ammonium regulates mTORC2 and mTORC1 signaling. Sci. Rep. 7, 44602 (2017).

3.Wang, A., Huen, S.C., Luan, H.H., et al. Opposing effects of fasting metabolism on tissue tolerance in bacterial and viral inflammation. Cell 166(6), 1512-1525 (2016).

来源：https://www.amyjet.com/products/10522-10.shtml