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Chemical Structure| 67526-95-8 Chemical Structure| 67526-95-8

Structure of Thapsigargin
CAS No.: 67526-95-8

Chemical Structure| 67526-95-8

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Thapsigargin, an inducer of endoplasmic reticulum (ER) stress, is an inhibitor of microsomal Ca2+-ATPase. Thapsigargin efficiently inhibits the replication of coronaviruses (HCoV-229E, MERS-CoV, SARS-CoV-2) in various cell types.

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Product Details of Thapsigargin

CAS No. :67526-95-8
Formula : C34H50O12
M.W : 650.75
SMILES Code : CCCCCCCC(O[C@@H]1[C@@H](OC(/C(C)=C\C)=O)C(C)=C2[C@@]1([H])[C@@](C)(OC(C)=O)C[C@H](OC(CCC)=O)[C@@]([C@@]3(O)C)(O)[C@@]2([H])OC3=O)=O
MDL No. :MFCD00083511
InChI Key :IXFPJGBNCFXKPI-FSIHEZPISA-N
Pubchem ID :446378

Safety of Thapsigargin

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H315-H319-H334-H335
Precautionary Statements:P261-P264-P271-P280-P284-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P342+P311-P403+P233-P405-P501

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Mouse primary gastric cell cultures 1 μM 3 hours To investigate the effect of Ca2+i release on Shh gene expression, results showed that thapsigargin significantly induced Shh expression at 3 hours. Gastroenterology. 2010 Dec;139(6):2061-2071.e2.
mIMCD-3 cells 1.0 μM Thapsigargin induced an increase in intracellular calcium concentration, indicating that it causes ER calcium release by inhibiting sarco/ER Ca2+-ATPase. Nat Commun. 2016 Jan 20;7:10330.
human scleral fibroblasts 10 µM 24 h To investigate the effect of ER stress on collagen gene expression, results showed that Col4a3, Col8a2, Col11a2, and Col15a1 genes were significantly upregulated, and Col1a1 expression was downregulated. Nat Commun. 2022 Oct 10;13(1):5859.
3T3-L1 adipocytes 0, 1, or 10 nM 0, 12, or 24 h To investigate the effect of ER stress on adipsin expression, it was found that thapsigargin significantly reduced the mRNA and protein expression of adipsin in a dose- and time-dependent manner. Biomolecules. 2020 Feb 17;10(2):314.
mouse primary hepatocytes (MPH) 1 µM 4 h To study the effect of endoplasmic reticulum stress (ERS) on hepatic molecular identity, it was found that ERS leads to loss of hepatic molecular identity. Mol Syst Biol. 2020 May;16(5):e9156.
HepG2 cells 5 μM 24 h Thapsigargin blocked the interaction between ER IGF-1R b and SERCA2, thereby inhibiting the growth of HCC cells. Acta Pharm Sin B. 2023 Sep;13(9):3744-3755.
Hep3B cells 5 μM 24 h Thapsigargin blocked the interaction between ER IGF-1R b and SERCA2, thereby inhibiting the growth of HCC cells. Acta Pharm Sin B. 2023 Sep;13(9):3744-3755.
MIN6 cells 1 µM 5 min At low glucose, thapsigargin-induced ER Ca2+ release was sufficient to induce NFATc3 activation and nuclear translocation. Mol Metab. 2022 Mar;57:101430.
Mouse islets 1 µM 5 min At low glucose, thapsigargin-induced ER Ca2+ release was sufficient to induce NFATc3 activation and nuclear translocation. Mol Metab. 2022 Mar;57:101430.
Human islets 1 µM 5 min At low glucose, thapsigargin-induced ER Ca2+ release was sufficient to induce NFATc3 activation and nuclear translocation. Mol Metab. 2022 Mar;57:101430.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Acute diastolic dysfunction model Intraperitoneal injection 0.75 mg/kg Single dose, echocardiography performed 5 hours post-treatment To evaluate the effect of Thapsigargin on diastolic function in mice, results showed significant prolongation of IVRT and decrease in reverse longitudinal strain rate, indicating impaired diastolic function J Mol Cell Cardiol. 2018 Jan;114:20-28
Mice Not specified Intraperitoneal injection 0.5 μg/g Single injection, killed 24 or 48 hours later Thapsigargin induced ER stress in mice, leading to increased expression of LCN2. Nat Commun. 2016 Jan 20;7:10330.
C57BL6J mice Myopia model Ocular administration 10 µM Single administration To investigate the effect of the ER stress inducer Thapsigargin on myopia development, results showed that Thapsigargin induced myopic changes. Nat Commun. 2022 Oct 10;13(1):5859.
C57BL/6N mice Obesity model Intraperitoneal injection 1 mg/kg Single injection, sacrificed after 6 hours To investigate the effect of acute ER stress on adipsin expression, it was found that thapsigargin significantly reduced the mRNA and protein expression of adipsin and increased the expression of ER stress markers. Biomolecules. 2020 Feb 17;10(2):314.
Nude mice HepG2 xenograft model Caudal vein injection 10 mg/kg Once daily for three consecutive weeks Thapsigargin inhibited the growth of HepG2 xenografts and reduced the formation of tumor nodules. Acta Pharm Sin B. 2023 Sep;13(9):3744-3755.
Mice C57BL/6J mice and ob/ob mice Intraperitoneal injection 0.5 mg/kg 2 days Thapsigargin was used to induce ER stress in mice adipose tissue to study its effects on autophagy and inflammation. The results showed that Thapsigargin treatment significantly increased the protein levels of autophagy markers LC3II, Beclin1, and Atg5, while decreasing the protein level of SQSTM1, indicating that Thapsigargin induced autophagy. Additionally, Thapsigargin promoted the secretion of inflammatory cytokines such as IL-18 and IL-1β. Front Immunol. 2017 Nov 8;8:1507

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01056029 Advanced Solid Tumors Phase 1 Completed - United States, Maryland ... More >> Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland, United States, 21231 United States, Texas University of Texas, Health Science Center,Cancer Therapy and Research Center San Antonio, Texas, United States, 78229 United States, Wisconsin University of Wisconsin Paul P Carbone Comprehensive Cancer Center Madison, Wisconsin, United States, 53792 Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.54mL

0.31mL

0.15mL

7.68mL

1.54mL

0.77mL

15.37mL

3.07mL

1.54mL

References

 

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