Abstract 2599: Inhibitory effects of new 1H-pyrrolo[3,2-c]pyridine derivative, KIST101029, on AP-1 activity and neoplastic cell transformation induced by insulin-like growth factor 1.

Abstract

Abstract Diarylureas and diarylamides derivatives are reported to have antitumor activity. Encouraged by the interesting antiproliferative activity of diarylurea and diarylamide derivatives, we synthesized a new series of diarylureas and diarylamides containing pyrrolo[3,2-c]pyridine scaffold. In this study, we demonstrate that a new 1H-pyrrolo[3,2-c]pyridine derivative, KIST101029, inhibits neoplastic cell transformation induced by insulin-like growth factor 1 (IGF-1) in mouse epidermal JB6 Cl41 cells. The KIST101029 compound inhibited mitogen-activated protein kinase/extracellular signal-regulated kinase kinases (MEK), c-jun N-terminal kinases (JNK), and mechanistic target of rapamycin (mTOR) signaling pathways induced by IGF-1 in JB6 Cl41 cells, resulting in the inhibition of c-fos and c-jun transcriptional activity. In addition, the KIST101029 inhibited the associated activator protein-1 (AP-1) transactivation activity and cell transformation induced by IGF-1 in JB6 Cl41 cells. Consistent with these observations, in vivo chorioallantoic membrane assay also showed that the KIST101029 inhibited IGF-1-induced tumorigenicity of JB6 Cl41 cells. Taken together, these results indicate that a new 1H-pyrrolo[3,2-c]pyridine derivative, KIST101029, might exert chemopreventive effects through the inhibition of phosphorylation of MAPK and mTOR signaling pathway. Citation Format: Hyo Jeong Yun, Hong Seok Choi. Inhibitory effects of new 1H-pyrrolo[3,2-c]pyridine derivative, KIST101029, on AP-1 activity and neoplastic cell transformation induced by insulin-like growth factor 1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2599. doi:10.1158/1538-7445.AM2013-2599 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.