B6614-1mg | Thapsigargin [67526-95-8] Clinisciences

Background

Thapsigargin is an inhibitor of microsomal Ca2+-ATPase, Thapsigargin inhibits the carbachol-evoked [Ca2+]i-transients with IC50 value of 0.353 nM[1].

Thapsigargin may induce cell apoptosis in MH7A cells in a time- and dose-dependent manner, and the percentages of cell death reached 44.6% at thapsigargin concentration of 1 μM treated for 4 days compared to the control. The protein and mRNA levels of cyclin D1 decreased gradually with the increasing of thapsigargin concentration and treatment times[2].

In regards to vivo results, tunicamycin is superior in not only inducing ER stress but also recapturing the metabolic alterations associated with ER stress[3].

References:

[1].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.

[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]. Abdullahi A, et al. Modeling Acute ER Stress in Vivo and in Vitro. Shock. 2017 Apr;47(4):506-513.

Product Citation

1. Xiao Yang, Tangjun Zhou, et al. "Loss of DDRGK1 impairs IRE1α UFMylation in spondyloepiphyseal dysplasia." Int J Biol Sci. 2023 Sep 4;19(15):4709-4725. PMID: 37781516
2. Zhenhua Feng, Siyue Tao, et al. "The deubiquitinase UCHL1 negatively controls osteoclastogenesis by regulating TAZ/NFATC1 signalling." Int J Biol Sci. 2023 Apr 24;19(8):2319-2332. PMID: 37215988
3. Jiayin Chang, Shihai Yan, et al. "The interaction between Hsp90-mediated unfolded protein response and autophagy contributes to As3+/Se4+ combination-induced apoptosis of acute promyelocytic leukemia cells." Toxicol Appl Pharmacol. 2023 May 15:467:116511. PMID: 37031722
4. Nana Yan, Yongqiang Wang, et al. "Stromal Interaction Molecule 1 Promotes the Replication of vvIBDV by Mobilizing Ca2+ in the ER." Viruses. 2022 Jul 13;14(7):1524. PMID: 35891504
5. Xinfeng Liu, Lu Wang, et al. "Mel1b and Mel1c melatonin receptors mediate green light-induced secretion of growth hormone in chick adenohypophysis cells via the AC/PKA and ERK1/2 signalling pathways." J Photochem Photobiol B. 2021 Dec;225:112322. PMID: 34736066
6. KE PENG, AIQIN SUN, et al. "Restoration of the ATG5‑dependent autophagy sensitizes DU145 prostate cancer cells to chemotherapeutic drugs." Oncol Lett. 2021 Sep;22(3):638. PMID: 34386060
7. Xu H, Liu P, et al. "FKBP9 promotes the malignant behavior of glioblastoma cells and confers resistance to endoplasmic reticulum stress inducers." J Exp Clin Cancer Res. 2020;39(1):44. Published 2020 Feb 28. PMID: 32111229
8. Qin W, Wu X, et al. "Suhuang antitussive capsule inhibits NLRP3 inflammasome activation and ameliorates pulmonary dysfunction via suppression of endoplasmic reticulum stress in cough variant asthma." Biomed Pharmacother. 2019 Jul 14;118:109188. PMID: 31315072
9. Chou CK, Liu W, et al. "Ethyl Acetate Extract of Scindapsus cf. hederaceus Exerts the Inhibitory Bioactivity on Human Non-Small Cell Lung Cancer Cells through Modulating ER Stress." Int J Mol Sci. 2018 Jun 21;19(7). pii: E1832. PMID: 29933620

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Chemical Properties

Physical Appearance	A crystalline solid
Storage	Desiccate at -20°C
M.Wt	650.76
Cas No.	67526-95-8
Formula	C₃₄H₅₀O₁₂
Solubility	≥39.2 mg/mL in DMSO; ≥24.8 mg/mL in EtOH; ≥4.12 mg/mL in H2O with ultrasonic
Chemical Name	(3S,3aR,4S,6S,6aR,7S,8S,9bS)-6-acetoxy-4-(butyryloxy)-3,3a-dihydroxy-3,6,9-trimethyl-8-(((Z)-2-methylbut-2-enoyl)oxy)-2-oxo-2,3,3a,4,5,6,6a,7,8,9b-decahydroazuleno[4,5-b]furan-7-yl octanoate
SDF	Download SDF
Canonical SMILES	O[C@@]([C@H]1OC(CCC)=O)([C@]2(C)O)[C@H](C([C@H]([C@@H]3OC(CCCCCCC)=O)[C@@](C1)(C)OC(C)=O)=C(C)[C@@H]3OC(/C(C)=C\C)=O)OC2=O
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment [1,2]:
Cell lines	NG115-401L neural cell line, isolated rat hepatocytes
Preparation method	The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	ED50: ～20 nM (NG115-401L neural cell line); ED50 ～80 nM (isolated rat hepatocytes)
Applications	Thapsigargin stimulated a rapid (within 15 s) transient increase in intracellular [Ca2+] in the NG115-401L neural cell line with the ED50 of around 20 nM. In isolated rat hepatocytes, Thapsigargin increased [Ca2+] in a rapid and dose-dependent manner, with an ED50 value of ～80 nM.
Animal experiment [3]:
Animal models	Male C57BL/6 mice with transient middle cerebral artery occlusion (tMCAO)
Dosage form	IC50: 2 to 20 ng, icv injection
Application	Thapsigargin dose-dependently reduced the brain infarct. Thapsigargin (TG) protected mice against ischemia-reperfusion-induced brain injury.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Jackson T R, Patterson S I, Thastrup O, et al. A novel tumour promoter, thapsigargin, transiently increases cytoplasmic free Ca2+ without generation of inositol phosphates in NG115-401L neuronal cells[J]. Biochemical Journal, 1988, 253(1): 81-86. [2]. Thastrup O, Cullen P J, Drbak B K, et al. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2 (+)-ATPase[J]. Proceedings of the National Academy of Sciences, 1990, 87(7): 2466-2470. [3]. Zhang X, Yuan Y, Jiang L, et al. Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury: Involvement of PARK2-dependent mitophagy[J]. Autophagy, 2014, 10(10): 1801-1813.