Thapsigargin (Synonyms: 毒胡蘿卜素)
Thapsigargin，內(nèi)質(zhì)網(wǎng)應(yīng)激誘導(dǎo)劑， 是一種微粒體 Ca2+-ATPase 抑制劑。Thapsigargin 能有效抑制不同細胞類型的冠狀病毒 (HCoV-229E、MERS-CoV、SARS-CoV-2) 復(fù)制。
生物活性
Thapsigargin, an endoplasmic reticulum (ER) stress inducer, is an inhibitor of microsomal Ca2+-ATPase. Thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types[1][2][3][4][5].
IC50 & Target
Ca2+-ATPase[1]
體外研究(In Vitro)
Thapsigargin (0.001-?1 μM; for 2 and 4 days) arrests cell proliferations in MH7A human rheumatoid arthritis synovial cells in a time- and dose-dependent manner[2].
Thapsigargin (0.001-?1 μM; for 2 and 4 days) induces cell apoptosis in MH7A cells in a time- and dose-dependent manner[2].
Thapsigargin (0.001-?1 μM; for 2 and 4 days) impairs mTOR activity and leads to cyclin D1 expressions in MH7A cells[2].
Thapsigargin inhibits Ca2+ entry into human neutrophil granulocytes[1].
Thapsigargin inhibits the carbachol-evoked [Ca2+]i-transients with (IC50=0.353 nM) or without (IC50=0.448 nM) a KCl-prestimulation, but an additional small component, with a much lower sensitivity (IC50=4814 nM), is observed in the absence of a KCl-prestimulation. In contrast, the KCl-evoked [Ca2+]i-transients displayed only one component with a very low sensitivity to Thapsigargin in both absence (IC50=3343 nM) and presence (IC50=6858 nM) of a carbachol-prestimulation[3].
Thapsigargin also phosphorylate p38 MAPK by Ca2+ influx through SOCE, leading to suppression of TNF-α-induced NF-κB phosphorylation.[6].
Cell Proliferation Assay[2]
| Cell Line: | MH7A human rheumatoid arthritis synovial cells |
| Concentration: | 0.001, 0.1, and 1?μM |
| Incubation Time: | For 2 and 4 days |
| Result: | Arrested cell proliferations in a time- and dose-dependent manner. |
體內(nèi)研究(In Vivo)
Thapsigargin (Injection; 0.25 ug/g, 0.5 ug/g and 1 ug/g; 24 hours) significant increases of 2 to 5-fold in chemokine and pro-inflammatory expression. Thapsigargin is more sensitive to inducing a systemic immune response[4]
| Animal Model: | Male Balb/c mice (20-25 g)[4] |
| Dosage: | 0.25 ug/g, 0.5 ug/g and 1 ug/g |
| Administration: | Injection; 24 hours |
| Result: | Increased of 2 to 5-fold in chemokine and pro-inflammatory expression. |
分子量：650.75
Formula：C34H50O12
CAS 號：67526-95-8
中文名稱：毒胡蘿卜素；毒胡蘿卜內(nèi)酯
運輸條件：Room temperature in continental US; may vary elsewhere.
儲存方式
-20°C, sealed storage, away from moisture and light
*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
溶解性數(shù)據(jù)
DMSO : 100 mg/mL (153.67 mM; Need ultrasonic)
| 濃度溶劑體積質(zhì)量 | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.5367 mL | 7.6834 mL | 15.3669 mL |
| 5 mM | 0.3073 mL | 1.5367 mL | 3.0734 mL |
| 10 mM | 0.1537 mL | 0.7683 mL | 1.5367 mL |
請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)。-80°C 儲存時，請在 6 個月內(nèi)使用，-20°C 儲存時，請在 1 個月內(nèi)使用。
以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：
——為保證實驗結(jié)果的可靠性，澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用； 以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶
- 1.
請依序添加每種溶劑： 10% DMSO 90% saline
Solubility: 5 mg/mL (7.68 mM); Suspended solution; Need ultrasonic
- 2.
請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (3.20 mM); Clear solution
- 3.
請依序添加每種溶劑： 10% DMSO 90% corn
參考文獻
[1]. Geiszt M, et al. Thapsigargin inhibits Ca2+ entry into human neutrophil granulocytes. Biochem J. 1995 Jan 15;305 ( Pt 2):525-8.
[2]. Wang H, et al. Effects of thapsigargin on the proliferation and survival of human rheumatoid arthritis synovialcells. ScientificWorldJournal. 2014 Feb 9;2014:605416.
[3]. Garavito-Aguilar ZV, et al. Differential thapsigargin-sensitivities and interaction of Ca2+ stores in human SH-SY5Y neuroblastoma cells. Brain Res. 2004 Jun 18;1011(2):177-86.
[4]. Abdullahi A, et al. Modeling Acute ER Stress in Vivo and in Vitro. Shock. 2017 Apr;47(4):506-513.
[5]. Mohammed Samer Shaban, et al. Inhibiting coronavirus replication in cultured cells by chemical ER stress. bioRxiv 2020.08.26.266304;
[6]. Junsuke Uwada, et al. Store-operated calcium entry (SOCE) contributes to phosphorylation of p38 MAPK and suppression of TNF-α signalling in the intestinal epithelial cells. Cell Signal. 2019 Nov;63:109358.
注：產(chǎn)品僅用于科研
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