thapsigargin

Thapsigargin 属于天然产物，是一种肌 内质网 Ca2+ ATP 酶 (SERCA) 的抑制剂，也是一种内质网应激诱导剂。Thapsigargin 通过阻断细胞将钙泵入肌浆和内质网的能力来提高胞浆钙浓度。

Pyr6 (N-[4-[3,5-Bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-3-fluoro-4-pyridinecarboxamide)是选择性的 TRPC3抑制剂，IC50值为0.49uM。

FKGK 18 is an inhibitor of group VIA (GVIA) calcium-independent phospholipase A2 (iPLA2). It inhibits GVIA iPLA2 by 99.9% at 0.091 mole fraction in a mixed micelle activity assay and is selective for GVIA iPLA2 over GIVA cPLA2 and GV sPLA2 where it shows 80.8 and 36.8% inhibition, respectively. FKGK 18 inhibits iPLA2β activity in cytosolic extracts from INS-1 cells overexpressing iPLA2β (IC50 = ~50 nM) as well as iPLA2γ activity in mouse heart membrane fractions (IC50s = ~1-3 μM). It inhibits glucose-induced increases in prostaglandin E2 production and insulin secretion in human pancreatic islets when used at a concentration of 10 μM and inhibits thapsigargin-induced apoptosis in INS-1 cells overexpressing iPLA2β in a concentration-dependent manner. FKGK 18 (20 mg/kg, 3 times per week) reduces blood glucose levels in an intraperitoneal glucose tolerance test, decreases the incidence of diabetes, and increases serum insulin levels in non-obese diabetic (NOD) mice.

Trilobolide is a natural counterpart of thapsigargin and an activator of cytokine secretion.

Azumolene sodium anhydrous is a muscle relaxant that inhibits the release of calcium from skeletal muscle sarcoplasmic reticulum. Azumolene inhibits a component of store-operated calcium entry coupled to the skeletal muscle ryanodine receptor. Azumolene, an equipotent dantrolene analog, inhibits a component of SOCE coupled to activation of RyR1 by caffeine and ryanodine, whereas the SOCE component induced by thapsigargin is not affected.

Soluble epoxide hydrolase (sEH) PROTAC 1a是一种利用蛋白质降解靶向嵌合体(PROTAC)技术，通过连接区域将cereblon配体1与sEH抑制剂t-TUCB结合。该化合物通过促进sEH的降解，特异性抑制sEH的水解酶活性(IC50 = 0.8 nM)，相较于其磷酸酶活性(IC50 = >10,000 nM)具有较高选择性。sEH PROTAC 1a还特定促进细胞质中而非过氧体中的sEH降解，并通过溶酶体而非蛋白酶体实现其降解。它能够降低thapsigargin诱导的HepG2与293T细胞中磷酸化的inositol-requiring enzyme 1α (IRE1α)水平和X-box结合蛋白1 (XBP1)剪接，表明能减少ER应激。

ATF4-IN-1 (Compound 21) 作为一种ATF4抑制剂，能够有效抑制Thapsigargin激活的HEK-293T细胞中的ATF4表达，其IC50为32.43 nM。此外，ATF4-IN-1的抑制活性优于ISRIB，并在HEK-293T细胞上展示出较低的细胞毒性（IC50为96 μM）。因其这些特性，ATF4-IN-1常被用于神经退行性疾病的研究。