The estrogen-related receptor α (ERRα) is an orphan nuclear receptor that can be regulated by peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1). XCT790 is a selective inverse agonist for ERRα with an IC50 value of 0.37 μM, but displays no activity against ERRγ and estrogen receptors ERα and ERβ[3]. XCT-790 at 5 – 20 μM reduced the viability of HepG2 and R-HepG2 cells in a dose-dependent manner. The treatment of HepG2 and R-HepG2 cells with XCT-790 (10 μM) for 24 h reduced the protein levels of ERRα and decreased mitochondrial masses as compared to the DMSO-treated control group[4]. In mice inoculated with H295R adrenocortical cancer cells, the administration of XCT790 (2.5 mg/kg) for 21 days decreased H295R cell proliferation and suppressed tumor growth compared to the vehicle-treated group[5].
作用机制
XCT790 is a thiadiazoleacrylamide that functions as a potent inverse agonist of ERRα[3].
XCT790 inhibited VSV-G protein expression, showing antiviral activity.
PLoS Pathog. 2017 Jun 7;13(6):e1006347.
human valvular interstitial cells (hVICs)
6 µg/mL
8 h
To evaluate the inhibitory effect of XCT790 on osteogenic differentiation of hVICs, results showed that XCT790 significantly reduced the expression of ALP and RUNX2, and inhibited calcium deposition.
Nat Commun. 2024 Jan 16;15(1):557.
human valvular interstitial cells (hVICs)
20 µg/mL
8 h
To evaluate the inhibitory effect of XCT790 on osteogenic differentiation of hVICs, results showed that XCT790 significantly reduced the expression of ALP and RUNX2, and inhibited calcium deposition.
Nat Commun. 2024 Jan 16;15(1):557.
HCT-116 cells
2.5, 5, 10 μM
30 h
XCT790 treatment resulted in ERRα degradation and inhibited migration of HCT-116 cells.
Cancer Res. 2010 Nov 15;70(22):9298-308.
PC-3 cells
2.5, 5, 10 μM
30 h
XCT790 treatment resulted in ERRα degradation and inhibited migration of PC-3 cells.
Cancer Res. 2010 Nov 15;70(22):9298-308.
MDA-MB 436 cells
2.5, 5, 10 μM
30 h
XCT790 treatment resulted in ERRα degradation and inhibited migration of MDA-MB 436 cells.
Cancer Res. 2010 Nov 15;70(22):9298-308.
MDA-MB 231 cells
2.5, 5, 10 μM
30 h
XCT790 treatment resulted in ERRα degradation and inhibited migration of MDA-MB 231 cells.
Cancer Res. 2010 Nov 15;70(22):9298-308.
Endometrial cancer cells
12.5 µM
48 h
XCT790 inhibits ERRα expression, reduces the proliferation of endometrial cancer cells, and enhances the therapeutic effect of carboplatin.
Cell Death Dis. 2025 Mar 17;16(1):182.
293T cells
2.5 μM
12 h
XCT790 significantly upregulated VSV-induced IFN-β and IFN-regulated gene expression and inhibited VSV production.
PLoS Pathog. 2017 Jun 7;13(6):e1006347.
HCT116 cells
1.5 µM
24 h
Induced EGFR expression, mimicking the effect of AM251
Br J Pharmacol. 2011 Oct;164(3):1026-40.
PANC-1 cells
1.5 µM
24 h
Induced HB-EGF and EGFR expression, mimicking the effect of AM251
Br J Pharmacol. 2011 Oct;164(3):1026-40.
XCT790 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
High-fat diet-induced aortic valve calcification model
Intravenous injection
600 µg/mouse
Once per week for 8 weeks
To evaluate the therapeutic effect of SR@PFeXCT on aortic valve calcification, results showed that SR@PFeXCT significantly alleviated aortic valve calcification and stenosis.
Nat Commun. 2024 Jan 16;15(1):557.
BALB/c nude mice
PC-9/GR xenograft model
Intraperitoneal injection
8 mg/kg
Daily for 21 days
XCT790 synergized with gefitinib to significantly inhibit the growth of PC-9/GR xenograft tumors
Mol Cancer. 2022 Mar 18;21(1):77
SCID mice
VCaP-CRPC xenograft model
Intraperitoneal injection
10 mg/kg
Once daily for 3 weeks
XCT790 treatment significantly inhibited tumor growth in the VCaP-CRPC xenograft model
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