Thapsigargin

Thapsigargin
Names
	IUPAC name (11S)-7,11-Dihydroxy-12-oxo-6β,12-epoxy-1β,7α,10α-guai-4-ene-2β,3α,8α,10-tetrayl 10-acetate 8-butanoate 3-[(2Z)-2-methylbut-2-enoate] 2-octanoate
	Systematic IUPAC name (3S,3aR,4S,6S,6aR,7S,8S,9bS)-3,3a-Dihydroxy-3,6,9-trimethyl-2-oxo-2,3,3a,4,5,6,6a,7,8,9b-decahydroazuleno[4,5-b]furan-4,6,7,8-tetrayl 6-acetate 4-butanoate 8-[(2Z)-2-methylbut-2-enoate] 7-octanoate
Identifiers
CAS Number	67526-95-8 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:9516 ;
ChEMBL	ChEMBL96926 ;
ChemSpider	393753 ;
ECHA InfoCard	100.116.539
IUPHAR/BPS	5351;
PubChem CID	446378;
UNII	Z96BQ26RZD ;
CompTox Dashboard (EPA)	DTXSID5040621 ;
	InChI 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 Key: IXFPJGBNCFXKPI-FSIHEZPISA-N ; InChI=1/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 Key: IXFPJGBNCFXKPI-FSIHEZPIBR;
	SMILES O=C3O[C@H]2C\1=C(\[C@H](OC(=O)\C(=C/C)C)[C@@H](OC(=O)CCCCCCC)[C@@H]/1[C@@](OC(=O)C)(C[C@H](OC(=O)CCC)[C@]2(O)[C@@]3(O)C)C)C;
Properties
Chemical formula	C34H50O12
Molar mass	650.762 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA). Structurally, thapsigargin is classified as a guaianolide, and is extracted from a plant, Thapsia garganica. It is a tumor promoter in mammalian cells.

Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. Store-depletion can secondarily activate plasma membrane calcium channels, allowing an influx of calcium into the cytosol. Depletion of ER calcium stores leads to ER stress and activation of the unfolded protein response. Non-resolved ER stress can cumulatively lead to cell death. Prolonged store depletion can protect against ferroptosis via remodeling of ER-synthesized phospholipids.

Thapsigargin treatment and the resulting ER calcium depletion inhibits autophagy independent of the UPR.

Thapsigargin is useful in experimentation examining the impacts of increasing cytosolic calcium concentrations and ER calcium depletion.

A study from the University of Nottingham showed promising results for its use against Covid-19 and other coronavirus.