Drug screening to target nuclear orphan receptor NR4A2 for cancer therapeutics.
Background: Our previous study suggested NR4A2, a subfamily member of orphan nuclear receptors, is essential for survival of human cancer cells such as mucoepidermoid carcinoma (MEC).
Methods: We conducted high throughput drug screening for NR4A2 inhibitors as a novel therapeutic modality. Positive screening was performed using a luciferase reporter vector containing NR4A2 binding sequence, and a CRE-reporter control vector was used to eliminate false positives. In vitro assays for positive hits were conducted.
Results: A total of 23 Food and Drug Administration (FDA) and 43 Life Science Library compounds were identified, including several epidermal growth factor inhibitors and Src inhibitors. Subsequent
Conclusions: Further research should focus on homologue selectivity,
Transl Lung Cancer Res
Komiya, Takefumi MD; Yamamoto, Satomi; Roy, Anuradha; McDonald, Peter; and Perez, Raymond P, "Drug screening to target nuclear orphan receptor NR4A2 for cancer therapeutics." (2017). PCI Publications and Projects. 16.