Yun, Hyo Jeong Kim, Garam Khanal, Prem Kim, Karam Oh, Chang-Hyun Choi, Hoo-Kyun Sohn, Honglae Choi, Hong Seok 2024-01-20T11:33:32Z 2024-01-20T11:33:32Z 2021-09-05 2013-09 0918-6158 https://pubs.kist.re.kr/handle/201004/127709 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 N-(3-(4-benzamido-1H-pyrrolo[3,2-c]pyridin-l-yl)phenyl)-4-morpholino-3-(trifluoromethyl)benzamide, KIST101029, inhibits neoplastic cell transformation induced by insulin-like growth factor 1 (IGF-1) in mouse epidermal JB6 C141 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 C141 cells, resulting in the inhibition of c-fos and c-mu 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 C141 cells. Consistent with these observations, in vivo chorioallantoic membrane assay also showed that the KIST101029 inhibited IGF-1-induced tumorigenicity of JB6 C141 cells. Importantly, KIST101029 suppressed the colony formation of A375 cells in soft agar. Taken together, these results indicate that a KIST101029 might exert chemopreventive effects through the inhibition of phosphorylation of MAPK and mTOR signaling pathway. English PHARMACEUTICAL SOC JAPAN RECEPTOR TYROSINE KINASES ADVANCED HEPATOCELLULAR-CARCINOMA MAP KINASE MULTIPLE-MYELOMA RAS ACTIVATION CANCER PATHWAYS MELANOMA SORAFENIB MUTATIONS Inhibitory Effects of a New 1H-Pyrrolo[3,2-c]pyridine Derivative, KIST101029, on Activator Protein-1 Activity and Neoplastic Cell Transformation Induced by Insulin-Like Growth Factor-1 Article 1 BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.36, no.9, pp.1466 - 1473 BIOLOGICAL & PHARMACEUTICAL BULLETIN 36 9 1466 1473 scie scopus 000323804900016 2-s2.0-84884650520 Pharmacology & Pharmacy Pharmacology & Pharmacy Article RECEPTOR TYROSINE KINASES ADVANCED HEPATOCELLULAR-CARCINOMA MAP KINASE MULTIPLE-MYELOMA RAS ACTIVATION CANCER PATHWAYS MELANOMA SORAFENIB MUTATIONS KIST101029 insulin-like growth factor 1 activator protein-1 cell transformation c-Fos c-Jun