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ATPase inhibitor
- Potent inhibitor of SERCA
- Cell-permeable tumor promoter
Thapsigargin is a potent inhibitor of sarco/endoplasmic reticulum Ca2+-ATPases (SERCA), which are linked with endoplasmic reticulum stress, and induces the release of intracellular stored Ca2+ without hydrolysis of inositolphospholipid (IC50=30nM). Inhibition of SERCA by thapsigargin reveals a significant change in intracellular Ca2+ homeostasis and pH regulation in tumor cells, and may be used to distinguish between discrete intracellular Ca2+ pools. Thapsigargin increases Ca2+-dependent Na+ influx in human platelets in a dose-dependent manner. Thapsigargin-induced tumor promotion and down-regulation of the EGF receptor is independent of PKC activation. Thapsigargin also stimulates nitric oxide (NO) production and as a result, may promote apoptosis.
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Product Details
| Appearance |
Colorless wax or white solid. |
|---|---|
| CAS |
67526-95-8 |
| Couple Target |
ATPase |
| Couple Type |
Inhibitor |
| Formula |
C34H50O12 |
| MI |
14: 9272 |
| MW |
650.8 |
| Purity |
≥95% (HPLC, TLC) |
| Solubility |
Soluble in acetone, DMSO (20mg/ml), or 100% ethanol (20mg/ml). |
| Source |
Isolated from Thapsia garganica. |
| Technical Info / Product Notes |
Replacement for ADI-908-298. |
Handling & Storage
| Use/Stability |
As indicated on product label or CoA when stored as recommended. Stable for at least 1 year after receipt when stored, as supplied, at -20°C. |
|---|---|
| Handling |
USE CAUTION – product is a tumor promoter. Solutions may lose activity after one week. For longer term storage, dissolve in acetone or ethanol, aliquot and evaporate solvent to dryness with a stream of nitrogen or argon. Store aliquots of neat compound at -20°C or colder. Protect from light and oxygen. |
| Long Term Storage |
-20°C |
| Shipping |
Ambient Temperature |
| Regulatory Status |
RUO – Research Use Only |
|---|
- TMEM65 regulates and is required for NCLX-dependent mitochondrial calcium efflux: Garbincius, J. F., Salik, O., et al.; Nat. Metab. 7, 714 (2025), Abstract
- Dependence of mitochondrial calcium signalling and dynamics on the disaggregase, CLPB: D’Angelo, D., Sánchez-Vázquez, V. H., et al.; Nat. Commun. 16, 2810 (2025), Abstract
- The endoplasmic reticulum pool of Bcl-xL prevents cell death through IP3R-dependent calcium release: R. Gadet, et al.; Cell Death Discov. 10, 346 (2024), Abstract
- Adapting the endoplasmic reticulum proteostasis rescues epilepsy-associated NMDA receptor variants: Zhang, P. P., Benske, T. M., et al.; Acta Pharmacol. Sin. 45, 282 (2024), Abstract
- GABRA1frameshift variants impair GABAA receptor proteostasis: Williams, M. P., Wang, Y., et al.; bioRxiv , (2024)
- Pharmacological chaperones restore proteostasis of epilepsy-associated GABAA receptor variants: Wang, Y. J., Seibert, H., et al.; Pharmacol. Res. 208, 107356 (2024), Abstract
- TMEM65 regulates NCLX-dependent mitochondrial calcium efflux: Garbincius, J. F., Salik, O., et al.; bioRxiv , (2023)
- Mitophagy restricts BAX/BAK-independent, Parkin-mediated apoptosis: Quarato, G., Mari, L., et al.; Sci. Adv. 9, eadg8156 (2023), Abstract
- MICU1 controls the sensitivity of the mitochondrial Ca2+ uniporter to activators and inhibitors: Rodriguez-Prados, M., Huang, K. T., et al.; Cell Chem. Biol. 30, 606 (2023), Abstract
- PERK recruits E-Syt1 at ER–mitochondria contacts for mitochondrial lipid transport and respiration: M.L. Sassano, et al.; J. Cell Biol. 222, e202206008 (2023), Abstract
- A non-invasive system to monitor in vivo neural graft activity after spinal cord injury: K. Ago, et al.; Commun. Biol. 5, 803 (2022), Abstract
- ER stress-induced cell death proceeds independently of the TRAIL-R2 signaling axis in pancreatic β cells: C. Hagenlocher, et al.; Cell Death Dis. 8, 34 (2022), Abstract
- The alkalinizing, lysosomotropic agent ML-9 induces a pH-dependent depletion of ER Ca2+ stores in cellulo: M. Kerkhofs, et al.; Biochim. Biophys. Acta Mol. Cell Res. 1869, 119308 (2022), Abstract
- Ca2+-mediated mitochondrial inner membrane permeabilization induces cell death independently of Bax and Bak: G. Quarato, et al.; Cell Death Differ. 29, 1318 (2022), Abstract
- Diverse maturity-dependent and complementary anti-apoptotic brakes safeguard human iPSC-derived neurons from cell death: R. Wilkens, et al.; Cell Death Dis. 13, 887 (2022), Abstract — Full Text
- Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T-cell Acute Lymphoblastic Leukemia: M. Marchesini, et al.; Cell Chem. Biol. 27, 678 (2021), Abstract — Full Text
- Selenoprotein DIO2 is a regulator of mitochondrial function, morphology and UPRmt in human cardiomyocytes: N. Bomer, et al.; Int. J. Mol. Sci. 22, 11906 (2021), Abstract — Full Text
- ATPase inhibitory factor-1 disrupts mitochondrial Ca2+ handling and promotes pathological cardiac hypertrophy through CaMKIIδ: M. Pavez-Giani, et al.; Int. J. Mol. Sci. 22, 4427 (2021), Abstract — Full Text
- An inhibitor-mediated beta-cell dedifferentiation model reveals distinct roles for FoxO1 in glucagon repression and insulin maturation: T. Casteels, et al.; Mol. Metab. 54, 101329 (2021), Abstract — Full Text
- ACRBP (Sp32) is involved in priming sperm for the acrosome reaction and the binding of sperm to the zona pellucida in a porcine model: Y. Kato, et al.; PLoS One 16, e0251973 (2021), Abstract — Full Text
- Deletion of mFICD AMPylase alters cytokine secretion and affects visual short-term learning in vivo: N. McCaul, et al.; J. Biol. Chem. 297, 100991 (2021), Abstract
- A molecular mechanism for turning off IRE1α signaling during endoplasmic reticulum stress: X. Li, et al.; Cell Rep. 33, 108563 (2020), Abstract — Full Text
- Functional peroxisomes are essential for efficient cholesterol sensing and synthesis: K. Charles, et al.; Front Cell Dev Biol 8, 560266 (2020), Abstract — Full Text
- Proteome instability is a therapeutic vulnerability in mismatch repair deficient cancer: D. McGrail, et al.; Cancer Cell 37, 371 (2020), Abstract — Full Text
- Dynamic changes in complexes of IRE1α, PERK, and ATF6α during endoplasmic reticulum stress: Sundaram, A., Appathurai, S., et al.; Mol. Biol. Cell 29, 1376 (2018), Abstract
- Remodeling the endoplasmic reticulum proteostasis network restores proteostasis of pathogenic GABAA receptors: Y.L. Fu, et al.; PLoS One 13, e0207948 (2018), Abstract
- MICU1 Confers Protection from MCU-Dependent Manganese Toxicity: J. Wettmarchausen, et al.; Cell Rep. 25, 1425 (2018), Abstract
- Spatial Separation of Mitochondrial Calcium Uptake and Extrusion for Energy-Efficient Mitochondrial Calcium Signaling in the Heart: S. De La Fuente, et al.; Cell Rep. 24, 3099 (2018), Abstract
- MICU1 Interacts with the D-Ring of the MCU Pore to Control Its Ca2+ Flux and Sensitivity to Ru360: Paillard, M., Csordás, G., et al.; Mol. Cell 72, 778 (2018), Abstract
- Drug-perturbation-based stratification of blood cancer: S. Dietrich, et al.; J. Clin. Invest. 128, 427 (2017), Abstract — Full Text
- Dynamic changes in oligomeric complexes of UPR sensors induced by misfolded proteins in the ER: Sundaram, A., Appathurai, S., et al.; bioRxiv , (2017)
- Inhibition of the inflammatory response to stress by targeting interaction between PKR and its cellular activator PACT: Dabo, S., Maillard, P., et al.; Sci. Rep. 7, 16129 (2017), Abstract
- The Sec61 translocon limits IRE1α signaling during the unfolded protein response: Sundaram, A., Plumb, R., et al.; Elife 6, (2017), Abstract
- Endocytosis regulates TDP-43 toxicity and turnover: G. Liu, et al.; Nat. Commun. 8, 2092 (2017), Abstract — Full Text
- AMPK-independent inhibition of human macrophage ER stress response by AICAR: M. Boß, et al.; Sci. Rep. 6, 32111 (2016), Application(s): Cell culture, assessing ER stress responses in macrophages, Abstract — Full Text
- Stromal Interaction Molecule 1 Rescues Store-Operated Calcium Entry and Protects NG115-401L Cells Against Cell Death Induced by Endoplasmic Reticulum and Mitochondrial Oxidative Stress: C. Zhang, et al.; Neurochem. Int. 97, 137 (2016), Application(s): Cell culture, Abstract
- Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells: C.A. Tang, et al.; Cancer Res. 76, 2137 (2016), Application(s): Stimulated cells, Abstract — Full Text
- Comparative effects of nodularin and microcystin-LR in zebrafish: 2. Uptake and molecular effects in eleuthero-embryos and adult liver with focus on endoplasmic reticulum stress: S. Faltermann, et al.; Aquat. Toxicol. 171, 77 (2016), Application(s): Positive control for ER-stress induction, Abstract
- HERPUD1 protects against oxidative stress-induced apoptosis through downregulation of the inositol 1,4,5-trisphosphate receptor: F. Paredes, et al.; Free Radic. Biol. Med. 90, 206 (2016), Application(s): Cell culture , Abstract
- Unbiased Cell-based Screening in a Neuronal Cell Model of Batten Disease Highlights an Interaction between Ca2+ Homeostasis, Autophagy, and CLN3 Protein Function: Chandrachud, U., Walker, M. W., et al.; J. Biol. Chem. 290, 14361 (2015), Abstract
- Transient receptor potential canonical 1 (TRPC1) channels as regulators of sphingolipid- and VEGF receptor expression: implications for thyroid cancer cell migration and proliferation: M.Y. Asghar, et al.; J. Biol. Chem. 290, 16116 (2015), Application(s): Cell Culture, Abstract — Full Text
- Antitumor immunity triggered by melphalan is potentiated by melanoma cell surface-associated calreticulin: Dudek-Perić, A. M., Ferreira, G. B., et al.; Cancer Res. 75, 1603 (2015), Abstract
- ER localization is critical for DsbA-L to Suppress ER Stress and Adiponectin Down-Regulation in Adipocytes: M. Liu, et al.; J. Biol. Chem. 290, 10143 (2015), Application(s): Cell Culture, Abstract — Full Text
- Stress of endoplasmic reticulum modulates differentiation and lipogenesis of human adipocytes: M. Koc, et al.; Biochem. Biophys. Res. Commun. 460, 684 (2015), Application(s): Cell Culture, Abstract
- Camphene isolated from essential oil of Piper cernuum (Piperaceae) induces intrinsic apoptosis in melanoma cells and displays antitumor activity in vivo: N. Girola, et al.; Biochem. Biophys. Res. Commun. 467, 928 (2015), Application(s): Cell Culture, Abstract
- Unfolded protein response signaling by transcription factor XBP-1 regulates ADAM10 and is affected in Alzheimer’s disease: S. Reinhardt, et al.; FASEB J. 28, 978 (2014), Abstract
- Functional interaction of protein kinase CK2 and activating transcription factor 4 (ATF4), a key player in the cellular stress response: Ampofo, E., Sokolowsky, T., et al.; Biochim. Biophys. Acta 1833, 439 (2013), Abstract
- Activation of the unfolded protein response bypasses trastuzumab-mediated inhibition of the PI-3K pathway: Kumandan, S., Mahadevan, N. R., et al.; Cancer Lett. 329, 236 (2013), Abstract
- Endoplasmic reticulum calcium depletion impacts chaperone secretion, innate immunity, and phagocytic uptake of cells: Peters, L. R., Raghavan, M., et al.; J. Immunol. 187, 919 (2011), Abstract
- Relationship between membrane permeability and specificity of human secretory phospholipase A(2) isoforms during cell death: Nelson, J., Gibbons, E., et al.; Biochim. Biophys. Acta 1808, 1913 (2011), Abstract
- ER stress drives Lipocalin 2 upregulation in prostate cancer cells in an NF-κB-dependent manner: Mahadevan, N. R., Rodvold, J., et al.; BMC Cancer 11, 229 (2011), Abstract
- A screen for regulators of survival of motor neuron protein levels: Makhortova, N. R., Hayhurst, M., et al.; Nat. Chem. Biol. 7, 544 (2011), Abstract
- Autophagy-mediated insulin receptor down-regulation contributes to endoplasmic reticulum stress-induced insulin resistance: L. Zhou, et al.; Mol. Pharmacol. 76, 596 (2009), Abstract
- Ca2+-store-dependent and -independent reversal of Stim1 localization and function: Smyth, J. T., DeHaven, W. I., et al.; J. Cell Sci. 121, 762 (2008), Abstract
- Thapsigargin, a selective inhibitor of sarco-endoplasmic reticulum Ca2+ -ATPases, modulates nitric oxide production and cell death of primary rat hepatocytes in culture: N.K. Canova, et al.; Cell Biol. Toxicol. 23, 337 (2007), Abstract
- Changes in intracellular Ca2+ and pH in response to thapsigargin in human glioblastoma cells and normal astrocytes: G.G. Kovacs, et al.; Am. J. Physiol. Cell. Physiol. 289, C361 (2005), Abstract
- Apoptosis to necrosis switching downstream of apoptosome formation requires inhibition of both glycolysis and oxidative phosphorylation in a BCL-X(L)- and PKB/AKT-independent fashion: Gramaglia, D., Gentile, A., et al.; Cell Death Differ. 11, 342 (2004), Abstract
- Thapsigargin induces apoptosis in cultured human aortic smooth muscle cells: C. Peiro, et al.; J. Cardiovasc. Pharmacol. 36, 676 (2000), Abstract
- Thapsigargin induces a calmodulin/calcineurin-dependent apoptotic cascade responsible for the death of prostatic cancer cells: B. Tombal, et al.; Prostate 43, 303 (2000), Abstract
- Signal transduction of thapsigargin-induced apoptosis in osteoblast: H.J. Chae, et al.; Bone 25, 453 (1999), Abstract
- Nitric oxide is involved in apoptosis induced by thapsigargin in rat mesangial cells: A.M. Rodriguez-Lopez, et al.; Cell Physiol. Biochem. 9, 285 (1999), Abstract
- Baculovirus p35 and Z-VAD-fmk inhibit thapsigargin-induced apoptosis of breast cancer cells: X.M. Qi, et al.; Oncogene 15, 1207 (1997), Abstract
- Role of EGR-1 in thapsigargin-inducible apoptosis in the melanoma cell line A375-C6: S. Muthukkumar, et al.; Mol. Cell. Biol. 15, 6262 (1995), Abstract — Full Text
- The role of calcium, pH, and cell proliferation in the programmed (apoptotic) death of androgen-independent prostatic cancer cells induced by thapsigargin: Y. Furuya, et al.; Cancer Res. 54, 6167 (1994), Abstract
- Intracellular Ca2+ signals activate apoptosis in thymocytes: studies using the Ca(2+)-ATPase inhibitor thapsigargin: S. Jiang, et al.; Exp. Cell Res. 212, 84 (1994), Abstract
- Thapsigargin, a Ca(2+)-ATPase inhibitor, depletes the intracellular Ca2+ pool and induces apoptosis in human hepatoma cells: A. Tsukamoto & Y. Kaneko; Cell Biol. Int. 17, 969 (1993), Abstract
- Brefeldin A, thapsigargin, and AIF4- stimulate the accumulation of GRP78 mRNA in a cycloheximide dependent manner, whilst induction by hypoxia is independent of protein synthesis: B.D. Price, et al.; J. Cell. Physiol. 152, 545 (1992), Abstract
- Demonstration of two forms of calcium pumps by thapsigargin inhibition and radioimmunoblotting in platelet membrane vesicles: B. Papp, et al.; J. Biol. Chem. 266, 14593 (1991), Abstract
- Identification of intracellular calcium pools. Selective modification by thapsigargin: J.H. Bian, et al.; J. Biol. Chem. 266, 8801 (1991), Abstract
- Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase: O. Thastrup, et al.; Proc. Natl. Acad. Sci. USA 87, 2466 (1990), Abstract
- Activation of calcium entry by the tumor promoter thapsigargin in parotid acinar cells. Evidence that an intracellular calcium pool and not an inositol phosphate regulates calcium fluxes at the plasma membrane: H. Takemura, et al.; J. Biol. Chem. 264, 12266 (1989), Abstract
- Phosphorylation at threonine-654 is not required for negative regulation of the epidermal growth factor receptor by non-phorbol tumor promoters: B.A. Friedman, et al.; Proc. Natl. Acad. Sci. USA 86, 812 (1989), Abstract
- Thapsigargin, a novel promoter, phosphorylates the epidermal growth factor receptor at threonine 669: K. Takishima, et al.; Biochem. Biophys. Res. Commun. 157, 740 (1988), Abstract
- A novel tumour promoter, thapsigargin, transiently increases cytoplasmic free Ca2+ without generation of inositol phosphates in NG115-401L neuronal cells: T.R. Jackson, et al.; Biochem. J. 253, 81 (1988), Abstract
- Palytoxin is a non-12-O-tetradecanoylphorbol-13-acetate type tumor promoter in two-stage mouse skin carcinogenesis: H. Fujiki, et al.; Carcinogenesis 7, 707 (1986), Abstract
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