Cell lines

The human mammary epithelial cell line MCF7, H295R adrenocortical cancer cell line

Preparation method

The solubility of this compound in DMSO is limited. 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

1, 5, 10 μM for 1-48 h

Applications

XCT790 induced deactivation and proteasome degradation of estrogen receptor-related receptor-α(ERRα). XCT790 potentiated the ICI182,780-induced ERα degradation [1]. Moreover, XCT790 inhibited the proliferation and blocked G1/S transition of H295R adrenocortical cancer cell line [2].

Animal models

H295R cell xenograft tumors model

Dosage form

2.5 mg/kg, every other day for 21 days;

Applications

XCT790 reduced established H295R cell xenograft tumors growth and decreased H295R cells proliferation in vivo.

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.

XCT790 is an inverse agonist of Estrogen-related receptor alpha (ERRα) with IC50 value of 0.37μM [1].

XCT790 is a first and selective inverse agonist of ERRα. It does not significantly inhibit ERRγ, ERα and ERβ below 10μM. XCT790 is proved to bind ERRα within LBD [1].

As an agonist of ERRα, XCT790 is found to decrease mitochondrial masses as well as affect the mitochondrial membrane potential, results in a subsequent function dysregulation of mitochondrial. XCT790 also reduces the expression level of PGC-1α which is a coactivator of ERRα to regulate mitochondrial biogenesis. Additionally, XCT790 can induce cell death in human hepatocarcinoma cell lines. It reduces the viabilities of HepG2 and its MDR cell line R-HepG2, MES-SA/DX5 and MES-SA in a dose-dependent manner. The mechanism of causing cell death is that XCT790 induces apoptosis through inducing ROS and subsequent caspases activation [2].

References:
[1] Lu X, Peng L, Lv M, ding K. Recent advance in the design of small molecular modulators of estrogen-related receptors. Curr Pharm Des. 2012;18(23):3421-31.
[2] Wu F, Wang J, Wang Y, Kwok TT, Kong SK, Wong C. Estrogen-related receptor alpha (ERRalpha) inverse agonist XCT-790 induces cell death in chemotherapeutic resistant cancer cells. Chem Biol Interact. 2009 Oct 7;181(2):236-42.