Thapsigargin

Catalog No.S7895 Batch:S789501

Technical Data

Formula	C₃₄H₅₀O₁₂
Molecular Weight	650.75	CAS No.	67526-95-8
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (153.66 mM)
		Ethanol	100 mg/mL (153.66 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Thapsigargin is a potent, non-competitive inhibitor of the sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA) with IC50 of 0.353 nM or 0.448 nM for the carbachol-evoked [Ca2+]i-transients with or without a KCl-prestimulation. Thapsigargin induces cell apoptosis. Thapsigargin is extracted from a plant, Thapsia garganica.

Targets

SERCA ^[1]

In vitro

In human SH-SY5Y neuroblastoma cells, two distinct intracellular Ca²⁺ stores, a KCl-/caffeine-sensitive and a carbachol-/IP₃-sensitive store, are demonstrated previously. Thapsigargin (0.05 nM–20 μM) induces a [Ca²⁺]_i-transient. Thapsigargin inhibits the carbachol-evoked [Ca²⁺]_i-transients with (IC50 = 0.353 nM) or without (IC50 = 0.448 nM) a KCl-prestimulation.^[1] Thapsigargin is effective in inducing Endoplasmic Reticulum (ER) stress in hepatocytes.^[3]

In vivo

TG at a dose of 0.5 ug/g/body weight is safe and does not elicit any adverse effects on survival in mice. TG treatment in mice results in significant expression of ER stress markers ATF6 and eIF2α in adipose tissue. TG treatment in mice fails to induce the expression of most ER stress and UPR proteins in the liver.^[3]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Human SH-SY5Y neuroblastoma cells Concentrations 0.05 nM–20 μM Incubation Time 5 min Method The TG-treatment is conducted in several different modes as follows: (1) Applied prior to any stimulus: After a 5-min preincubation with 1.5 mM CaCl2, TG in different concentrations (0.05 nM–20 μM) is added to the cell suspension and the mixture is then incubated for further 5 min at 37 ℃. Stimulation starts with 100 mM KCl followed by 1 mM CAB or vice versa. (2) Applied between two stimuli: TG is added to cell suspension after the Ca²⁺-transient evoked by the first stimulant (100 mM KCl or 1 mM CAB) has reached its steady state. 5 min after the TG-addition, cells are then challenged for the second time by 1 mM CAB or 100 mM KCl. (3) Applied briefly after the first (KCl- or CAB-) stimulation: In this treatment mode, TG is added briefly ( ~ 10 s) after the first stimulant (100 mM KCl or 1 mM CAB) is applied, before the evoked [Ca²⁺]_i-transient reaches a new steady state. The second stimulant (1 mM CAB or 100 mM KCl) is then applied 5 min after the TG-addition. (4) Applied briefly after the second stimulation: In the CAB→KCl stimulation mode, TG is added briefly ( ~ 10 s) after the second stimulant, i.e. 100 mM KCl.
Animal Study:^{^[3]}	Animal Models Male Balb/c mice Dosages 0.5 mg/kg Administration IP

Cell Assay:^{^[1]}

Cell lines
Human SH-SY5Y neuroblastoma cells
Concentrations
0.05 nM–20 μM
Incubation Time
5 min
Method
The TG-treatment is conducted in several different modes as follows: (1) Applied prior to any stimulus: After a 5-min preincubation with 1.5 mM CaCl2, TG in different concentrations (0.05 nM–20 μM) is added to the cell suspension and the mixture is then incubated for further 5 min at 37 ℃. Stimulation starts with 100 mM KCl followed by 1 mM CAB or vice versa. (2) Applied between two stimuli: TG is added to cell suspension after the Ca²⁺-transient evoked by the first stimulant (100 mM KCl or 1 mM CAB) has reached its steady state. 5 min after the TG-addition, cells are then challenged for the second time by 1 mM CAB or 100 mM KCl. (3) Applied briefly after the first (KCl- or CAB-) stimulation: In this treatment mode, TG is added briefly ( ~ 10 s) after the first stimulant (100 mM KCl or 1 mM CAB) is applied, before the evoked [Ca²⁺]_i-transient reaches a new steady state. The second stimulant (1 mM CAB or 100 mM KCl) is then applied 5 min after the TG-addition. (4) Applied briefly after the second stimulation: In the CAB→KCl stimulation mode, TG is added briefly ( ~ 10 s) after the second stimulant, i.e. 100 mM KCl.

Animal Study:^{^[3]}

Animal Models
Male Balb/c mice
Dosages
0.5 mg/kg
Administration
IP

References

Selleck's Thapsigargin has been cited by 26 publications

Simultaneous proteome localization and turnover analysis reveals spatiotemporal features of protein homeostasis disruptions [ Nat Commun, 2024, 15(1):2207]	PubMed: 38467653
TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry [ Nat Commun, 2024, 15(1):2371]	PubMed: 38490996
Leptin-mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer [ Cancer Commun (Lond), 2024, 10.1002/cac2.12583]	PubMed: 38958445
Cetylpyridinium chloride triggers paraptosis to suppress pancreatic tumor growth via the ERN1-MAP3K5-p38 pathway [ iScience, 2024, 27(8):110598]	PubMed: 39211547
Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein response [ Cancer Cell Int, 2024, 24(1):38]	PubMed: 38238825
ER stress induces caspase-2-tBID-GSDME-dependent cell death in neurons lytically infected with herpes simplex virus type 2 [ EMBO J, 2023, e113118.]	PubMed: 37646198
Combination of RUNX1 inhibitor and gemcitabine mitigates chemo-resistance in pancreatic ductal adenocarcinoma by modulating BiP/PERK/eIF2α-axis-mediated endoplasmic reticulum stress [ J Exp Clin Cancer Res, 2023, 42(1):238]	PubMed: 37697370
Combination of RUNX1 inhibitor and gemcitabine mitigates chemo-resistance in pancreatic ductal adenocarcinoma by modulating BiP/PERK/eIF2α-axis-mediated endoplasmic reticulum stress [ J Exp Clin Cancer Res, 2023, 42(1):238]	PubMed: 37697370
HRS mediates tumor immune evasion by regulating proteostasis-associated interferon pathway activation [ Cell Rep, 2023, 10.1016/j.celrep.2023.113352]	PubMed: 37948180
Porcine reproductive and respiratory syndrome virus infection triggers autophagy via ER stress-induced calcium signaling to facilitate virus replication [ PLoS Pathog, 2023, 19(3):e1011295]	PubMed: 36972295

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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