CITCO, an imidazothiazole derivative, is a selective Constitutive androstane receptor (CAR) agonist. It inhibits growth and expansion of brain tumour stem cells (BTSCs) and has an EC50 of 49 nM over pregnane X receptor (PXR), and no activity on other nuclear receptors[1].
The constitutive androstane receptor (CAR) is a xenobiotic sensor expressed in hepatocytes that activates genes involved in drug metabolism, lipid homeostasis, and cell proliferation[1].
In vitro, CAR activation accelerated intestinal epithelial wound healing by enhancing cell migration[2].
CITCO, an imidazothiazole derivative, is a selective Constitutive androstane receptor (CAR) agonist. CITCO inhibits growth and expansion of brain tumour stem cells (BTSCs) and has an EC50 of 49 nM over pregnane X receptor (PXR). CITCO (1-50 μM; 48 hours) results in a dose-dependent inhibition of viable cell count and proliferation in both T98G and U87MG glioma and BTSCs. CITCO (2.5, 5 μM; 48 hours) induces cell cycle arrest differentially in different BTSCs in culture, but not in normal astrocytes. CITCO (2.5-10 μM; 48 hours) induces apoptosis in BTSCs in culture (dose dependently), and causes the T98G and U87MG glioma and BTSCs expressing very low levels of CAR protein. CITCO (intraperitoneal; on days 22, 24, 26, 30 and 36) with 25 μg results a significant decrease in tumour growth, which further decreases to an undetectable level after treatment with 100 μg CITCO[3].
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