PMID- 23748899
OWN - NLM
STAT- MEDLINE
DCOM- 20140401
LR  - 20190720
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 36
IP  - 9
DP  - 2013
TI  - 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.
PG  - 1466-73
AB  - 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-1-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 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. 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.
FAU - Yun, Hyo Jeong
AU  - Yun HJ
AD  - College of Pharmacy, Chosun University.
FAU - Kim, Garam
AU  - Kim G
FAU - Khanal, Prem
AU  - Khanal P
FAU - Kim, Karam
AU  - Kim K
FAU - Oh, Chang-Hyun
AU  - Oh CH
FAU - Choi, Hoo-Kyun
AU  - Choi HK
FAU - Sohn, Honglae
AU  - Sohn H
FAU - Choi, Hong Seok
AU  - Choi HS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130610
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 
      (N-(3-(4-benzamido-1H-pyrrolo(3,2-c)pyridin-1-yl)phenyl)-4-morpholino-3-(trifluoromethyl)benzamide)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Transcription Factor AP-1)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Benzamides/*pharmacology
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cell Transformation, Neoplastic/chemically induced/*drug effects/metabolism
MH  - Chickens
MH  - Chorioallantoic Membrane
MH  - Insulin-Like Growth Factor I
MH  - Mice
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Proto-Oncogene Proteins c-raf/*antagonists & inhibitors/metabolism
MH  - Transcription Factor AP-1/metabolism
EDAT- 2013/06/12 06:00
MHDA- 2014/04/02 06:00
CRDT- 2013/06/11 06:00
PHST- 2013/06/11 06:00 [entrez]
PHST- 2013/06/12 06:00 [pubmed]
PHST- 2014/04/02 06:00 [medline]
AID - DN/JST.JSTAGE/bpb/b13-00244 [pii]
AID - 10.1248/bpb.b13-00244 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2013;36(9):1466-73. doi: 10.1248/bpb.b13-00244. Epub 2013 Jun 
      10.