GSK5182 is an orally available 4-hydroxy-tamoxifen (4-OHT) analog and a high affinity estrogen receptor-related receptor γ (ERRγ) inverse agonist (68% inhibition at 1 µM by reporter assay) with 25-fold reduced affinity and little antagonistic activity toward ERRα (No inhibition against 100 nM estradiol-induced reporter activity up to 1 µM). GSK5182 effectively inhibits ERRγ-dependent gene expression and biological functions both in cultures (1-10 µM) and in various animal studies in vivo (10-80 mg/kg i.p. or p.o. in rats and mice).
Orally available, selective estrogen receptor-related receptor γ (ERRγ) inverse agonist with in vitro and in vivo efficacy.
Estrogen-related receptors (ERRs) are the first identified orphan nuclear receptors. The ERR family consists of ERRα, ERRβ, and ERRγ, regulating diverse isoform-specific functions. We have reported the importance of ERRγ in osteoarthritis (OA) pathogenesis. However, therapeutic approaches with ERRγ against
Midbrain dopaminergic (DAergic) neurotransmission plays a crucial role in regulating motor, cognitive, and emotional functions. The orphan nuclear receptor estrogen-related receptor gamma (ERRγ) is highly expressed in the adult brain and in the developing fetal brain. Our previous study showed
International journal of molecular sciences, 21(19) (2020-10-02)
Bone morphogenetic protein 6 (BMP6) is a multifunctional growth factor involved in organ development and homeostasis. BMP6 controls expression of the liver hormone, hepcidin, and thereby plays a crucial role in regulating iron homeostasis. BMP6 gene transcriptional regulation in liver
Brain derived neurotrophic factor (BDNF) promotes maturation of dopaminergic (DAergic) neurons in the midbrain and positively regulates their maintenance and outgrowth. Therefore, understanding the mechanisms regulating the BDNF signaling pathway in DAergic neurons may help discover potential therapeutic strategies for
Fibroblast growth factor 21 (FGF21), a stress inducible hepatokine, is synthesized in the liver and plays important roles in glucose and lipid metabolism. However, the mechanism of hepatic cannabinoid type 1 (CB1) receptor-mediated induction of FGF21 gene expression is largely
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