Thapsigargin

A Potent and Cell-Permeable Inhibitor of SERCA Pump Ca2+-ATPase/an Intracellular Ca2+ Mobilizer
    Cat #: T-650
  • Lyophilized Powder
  • Bioassay Tested
  • Origin Thapsia garganica.
    Source Natural
    MW: 650.7
    Purity: >99% (HPLC)
    Effective concentration 50 nM - 1 μM.
    Structure
    • Thapsigargin
    Chemical name (3S,3aR,4S,6S,6AR,7S,8S,9bS)-6-(Acetyloxy)-2,3,3a,4,5,6 ,6a,7,8,9b-decahydro-3,3a-dihydroxy-3,6,9-trimethyl-8-[ [(2Z)-2-methyl-1-oxo-2-butenyl]oxy]-2-oxo-4-(1-oxobutox y)azuleno[4,5-b]furan-7-yl octanoate.
    Molecular formula C34H50O12.
    CAS No.: 67526-95-8.
    Activity Thapsigargin is a highly potent inhibitor of the sarco-endoplasmic reticulum Ca2+-ATPases (SERCAs), inhibiting Ca2+ pumping to intracellular stores at nanomolar concentrations, with IC50 ranging from 0.2 nM to 50 nM in various mammalian cell types.1 Thapsigargin-induced depletion of Ca2+ stores leads to apoptosis in various cell lines.2-4
    References-Activity
    1. Rodriguez-Lopez, A.M. et al. (1999) Cell Physiol. Biochem9, 285.
    2. Wei, H. et al. (1998) J. Neurochem. 70, 2305.
    3. Waring, P. and Beaver, J. (1996) Exp. Cell. Res227, 264.
    4. Jackson, T.R. et al. (1988) Biochem. J253, 81.
    Shipping and storage Shipped at room temperature. Product as supplied can be stored intact at room temperature for several weeks. For longer periods, it should be stored at -20°C.
    Solubility DMSO, ethanol or acetone. Centrifuge all product preparations before use (10000 x g 5 min).
    Storage of solutions Up to one week at 4°C or three months at -20°C.
    Our bioassay
    • Thapsigargin
      Alomone Labs Thapsigargin induces cytosolic Ca2+ increase in Jurkat cells.
      Cells were loaded with Fluo-3-AM dye in the presence of 5 mM EGTA. 20 nM Thapsigargin (#T-650) application induces a significant increase in intracellular Ca2+. Changes in intracellular Ca2+ were detected as changes in Fluo-3 fluorescent emission following the application (arrow) of control or Thapsigargin.
    • Thapsigargin
      Alomone Labs Thapsigargin induces apoptosis in Jurkat cells.
      Cells were grown to 70% confluency. 1 μM Thapsigargin (#T-650) or vehicle was added for six hours. Cell extracts were then probed for cleaved Caspase 3 with specific antibodies.
    • Thapsigargin
      Alomone Labs Thapsigargin increases intracellular Ca2+ by modulating  the autophosphorylation of CaMK II in 3T3-L1 cells. 
      Cells were starved for 2h and then stimulated with 1 or 5 µM Thapsigargin (#T-650) for the indicated times. The cell extracts were blotted and probed with an antibody for phospho-(Thr268)-CAMKII (Calmodulin dependent kinase II).
    • Thapsigargin
      Alomone Labs Thapsigargin induces cytosolic Ca2+ increase in HEK 293 cells.
      Ca2+ traces from Fluo-3 AM loaded HEK 293 cells treated with 5 µM Thapsigargin (#T-650) in the presence of 5 mM EGTA.
    References - Scientific background
    1. Treiman, M. et al. (1998) Trends Pharmacol. Sci19, 131.
    2. Rodriguez-Lopez, A.M. et al. (1999) Cell Physiol. Biochem9, 285.
    3. Waring, P. and Beaver, J. (1996) Exp. Cell. Res227, 264.
    4. Wei, H. et al. (1998) J. Neurochem. 70, 2305.
    5. Christensen, S.B. et al. (1980) Tetrahedron Lett. 21, 3829.
    6. Christensen, S.B. et al. (1982) J. Org. Chem47, 649.
    7. Rasmussen, U. et al. (1978) Acta Pharm. Suec15, 133.
    8. Jackson, T.R. et al. (1988) Biochem. J253, 81.
    9. Sagara, Y. and Inesi, G. (1991) J. Biol. Chem266, 13503.
    10. Lytton, J. et al. (1991) J. Biol. Chem266, 17067.
    11. Takemura, H. et al. (1989) J. Biol. Chem264, 12266.
    12. Patkar, S.A. (1979) Agents Actions 9, 53.
    13. Ohuchi, K. et al. (1987) J. Cancer Res. Clin. Oncol. 113, 319.
    Scientific background Thapsigargin, derived from the plant genus Thapsia,1-3 is an extremely tight-binding inhibitor of intracellular Ca2+ pumps. It was initially described as a tumor promoting agent which induces rapid Ca2+ release from intracellular stores4 by inhibition of the sarcoplasmic/endoplasmic reticulum Ca2+-dependent ATPase pump without inositol phosphate formation.5-7 The thapsigargin induced depletion of Ca2+ stores causes apoptosis in most cell lines.8-10 It has also been shown to cause histamine secretion from rat mast cells,11 and to stimulate arachidonic acid metabolism in macrophages.12 Its tumour-promoting function probably results, at least partly, from cytotoxicity, causing a wound response in the skin.13 The tumorogenic activity of thapsigargin might be due to its activation of protein kinase B (Akt) which subsequently stimulates MAP kinase signaling via Src and Raf-1.12,13
    Target SERCA
    Image & Title ThapsigarginAlomone Labs Thapsigargin decreases Ca2+ signals in rat mossy fibers.Rat hippocampal slices were incubated with 10 µM Thapsigargin (#T-650) for 60 min. The Ca2+ signals from mossy fiber terminals decreased significantly after wash-in.Adapted from Liang, Y. et al. (2002) J. Neurophysiol. 87, 1132. with permission of The American Physiological Society.
    Last update: 24/01/2020

    Thapsigargin (#T-650) is a highly pure, natural and biologically active compound.

    For research purposes only, not for human use

    Applications

    Specifications

    Scientific Background

    Citations

    Citations
    Electrophysiology
    1. Mouse α-cells (single cell).
      Dickerson, M.T. et al. (2019) Am. J. Physiol. 316, E646.
    Product citations
    1. Kostic, M. et al. (2018) Cell Rep. 25, 3465.
    2. Maggio, N. and Vlachos, A. (2018) J. Mol. Med. 96, 1039.
    3. Smaardijk, K.S. et al. (2018) Biochim. Biophys. Acta Mol. Cell Res. 1865, 855.
    4. Whitt, J.P. et al. (2018) J. Gen. Physiol. 150, 259.
    5. Bittremieux, M. et al. (2017) Cell Calcium 62, 60.
    6. Chen, J. et al. (2017) J. Biol. Chem. 292, 6938.
    7. Fung-Leung, W.P. et al. (2017) PLoS ONE 12, e0170102.
    8. Makitani, K. et al. (2017) J. Pharmacol. Sci. 134, 37.
    9. Smaardijk, S. et al. (2017) Tissue Cell 49, 141.
    10. Vierra, N.C. et al. 92017) Sci. Signal. 10, eaan2883.
    11. Choi, S.Y. et al. (2016) PLoS ONE 11, e0150921.
    12. Landowski, L.M. et al. (2016) J. Biol. Chem. 291, 1092.
    13. Srivats, S. et al. (2016) J. Cell Biol. 213, 65.
    14. Murray, J.K. et al. (2015) J. Med. Chem. 58, 6784.
    15. Vutthasathien, P. and Wattanapermpool, J. (2015) J. Appl. Physiol. 119, 831.
    16. Mariqueo, T.A. et al. (2014) J. Neurophysiol. 111, 1940.
    17. Tamura, A. et al. (2014) PLoS ONE 9, e85351.
    18. Hooper, J.S. et al. (2013) Brain Res. 1503, 7.
    19. Lin, F.F. et al. (2013) J. Pharmacol. Exp. Ther. 345, 225.
    20. Munoz, E. et al. (2013) Cell Calcium 54, 375.
    21. Saleem, H. et al. (2013) PLoS ONE 8, e54877.
    22. Witayavanitkul, Net al. (2013) Am. J. Physiol. 304, H465.
    23. Bader, Pet al. (2012) Pflugers Arch. 464, 249.6251.
    24. Mitchell, C.Bet al. (2012) J. Neurochem. 122, 1155.
    25. Shpak, G. et al. (2012) J. Neurosci. 32, 6251.
    26. Korkotian, E. and Segal, M. (2011) J. Physiol. 589.24, 5987.
    27. Fekete, A. et al. (2009) J. Neurochem. 111, 745.
    28. Tanaka, M. et al. (2009) J. Neurosci. Res. 87, 820.
    29. Hall, A.A. et al. (2009) Glia 57, 744.
    30. Herrera, Yet al. (2008) J. Pharmacol. Exp. 327, 491.
    31. Fajardo, Oet al. (2008) J. Neurosci. 28, 7863.
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