艾美捷Thapsigargin毒胡蘿卜素化學(xué)性質(zhì)&體外研究
Thapsigargin?是一種有效的、非競(jìng)爭(zhēng)性的?the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)?的抑制劑，對(duì)carbachol誘導(dǎo)的[Ca2+]i瞬變?cè)诖娌淮嬖贙Cl預(yù)刺激條件下的IC50值分別為0.353 nM和0.448 nM。Thapsigargin?可誘導(dǎo)細(xì)胞凋亡。Thapsigargin?提取自植物Thapsia garganica。
艾美捷Thapsigargin技術(shù)信息：
正式名稱：
(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編號(hào)：67526-95-8
分子式：C34H50O12
公式重量：650.8
純度：≥97%
配方：結(jié)晶狀固體
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
運(yùn)輸和存儲(chǔ)信息：
儲(chǔ)存：-20°C
運(yùn)輸：美國(guó)大陸的室溫；其他地方可能有所不同
穩(wěn)定性：≥?4年
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艾美捷Thapsigargin體外研究：
Thapsigargin以時(shí)間和劑量依賴的方式阻止MH7A人類類風(fēng)濕性關(guān)節(jié)炎滑膜細(xì)胞的增殖。
Thapsigargin損害mTOR活性并導(dǎo)致MH7A細(xì)胞中細(xì)胞周期蛋白D1的表達(dá)。
Thapsigargin抑制Ca2+進(jìn)入人類中性粒細(xì)胞。
Thapsigargin在有（IC50=0.353 nM）或沒(méi)有（IC50=0.448 nM）KCl-prestimulation的情況下，都能抑制卡巴喬誘發(fā)的[Ca2+]i-transients，但在沒(méi)有KCl-prestimulation的情況下，觀察到另外一個(gè)小的成分，其敏感性要低很多（IC50=4814 nM）。相比之下，lv化物誘發(fā)的[Ca2+]i-transients只顯示了一個(gè)成分，在沒(méi)有（IC50=3343 nM）和有（IC50=6858 nM）卡巴膽刺激的情況下，對(duì)Thapsigargin的敏感性都非常低。
Thapsigargin還通過(guò)SOCE的Ca2+流入使p38 MAPK磷酸化，導(dǎo)致TNF-α誘導(dǎo)的NF-κB磷酸化受到抑制。
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艾美捷Thapsigargin文獻(xiàn)參考：
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).
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艾美捷Thapsigargin文獻(xiàn)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).
