Thapsigargin

Thapsigargin is an inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA, IC50 = ~30 nM for the rat liver microsomal enzyme), an ER stress inducer, and a sesquiterpene lactone that has been found in Thapsia. It increases intracellular calcium levels in isolated rat hepatocytes (EC50 = ~80 nM) and protein levels of the ER stress markers DNA damage-inducible transcript 3 (DDIT3), also known as CHOP, and glucose-regulated protein 78 kDa (GRP78), as well as phosphorylation of protein kinase R-like ER kinase (PERK) and eukaryotic translation initiation factor 2alpha subunit (eIF2alpha) in SH-SY5Y cells when used at a concentration of 1 µM. Acute exposure of thapsigargin (2 µg/ml for 1 h) to primary mouse bone marrow-derived macrophages (BMDMs) protects against TNF- and zVAD-induced necroptosis and prolonged exposure of thapsigargin (2-16 µM for 48 h) induces apoptosis in SW-13 adrenocortical carcinoma cells. Thapsigargin (3 µM) induces autophagosome accumulation in mouse embryonic fibroblasts (MEFs). It reduces viral titers in Vero E6 cells co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A strain H1N1 when used at a concentration of 0.5 µM. Thapsigargin (1 mg/kg) reduces tumor volume in an SW-13 mouse xenograft model.Formal Name: (3S,3aS,4R,6R,7S,8R)-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-decahydro-1H-cyclopenta[e]azulen-7-yl octanoate. CAS Number: 67526-95-8. Molecular Formula: C34H50O12. Formula Weight: 650.8. Purity: >97%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, Ethanol: 30 mg/ml, Ethanol:PBS (pH 7.2)(1:2): 0.3 mg/ml. SMILES: C[C@]1(OC(C)=O)C[C@H](OC(CCC)=O)[C@@]2(O)[C@](OC([C@@]2(C)O)=O)([H])C3=C(C)[C@H](OC(/C(C)=C\C)=O)[C@@H](OC(CCCCCCC)=O)C13. InChi Code: InChI=1S/C34H50O12/c1-9-12-13-14-15-17-24(37)43-28-26-25(20(5)27(28)44-30(38)19(4)11-3)29-34(41,33(8,40)31(39)45-29)22(42-23(36)16-10-2)18-32(26,7)46-21(6)35/h11,22,26-29,40-41H,9-10,12-18H2,1-8H3/b19-11-/t22-,26?,27-,28-,29-,32-,33+,34+/m0/s1. InChi Key: IXFPJGBNCFXKPI-JUVUYJTQSA-N. Origin: Plant/Thapsia garganica.