N-(3-Bromophenyl)-6,7-dimethoxy-4-quinazolinamine hydrochloride (AG 1517; NSC 669364; PD 153035; SU 5271; WHI-P79)
• extremely potent inhibitor of epidermal growth factor (EGF) receptor tyrosine kinase, with an IC50 of 25 pM. Inhibits other purified tyrosine kinases only at micromolar or higher concentrations
OTAVAchemicals Catalogue Number: 7020540711
CAS Registry Number: 153436-54-5
Purity: 95%+ (HPLC)
Ref.: Grunt et al. An EGF receptor inhibitor induces RAR-β expression in breast and ovarian cancer cells. Biochemical and Biophysical Research Communications (2005), 329, 1253-1259
Abstract: Inhibition of the epidermal growth factor (EGF)-receptor (EGFR) has become a promising anticancer treatment strategy. Application of retinoids yields encouraging results for cancer prevention and therapy. Many tumors express no or low amounts of retinoic acid receptor-β2 (RAR-β2) due to epigenetic silencing via DNA hypermethylation. RAR-β2 is the main mediator of the antiproliferative effect of retinoids. RAR-β2 re-expression causes reversal of transformation, cell cycle arrest, and restoration of retinoid sensitivity. RAR-β2 is thus a tumor suppressor. Western blotting, colorimetric in vitro cell proliferation assays, and reverse transcription-polymerase chain reaction demonstrated that the EGFR inhibitor PD153035 not only blocked activation of EGFR and inhibited cell growth, but also stimulated RAR-β expression in MDA-MB-468 breast and OVCAR-3 ovarian carcinoma cells. Upregulation of RAR-β by PD153035 was confirmed by real-time reverse transcription-polymerase chain reaction. In contrast, expression of other retinoid receptors and of estrogen receptor-α was not affected. PD153035-mediated re-induction of RAR-β was associated with demethylation of the RAR-β2 gene promoter P2 as demonstrated by methylation-specific polymerase chain reaction. These novel results on the ErbB/retinoid receptor cross-talk may be useful for designing future anticancer combination regimens.