Potent osteogenic activity of a novel imidazobenzimidazole derivative, IBIP

Su Jung Bae, Yong Ki Min, Eun Sook Hwang

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2 Scopus citations


Bone mass is controlled by a balance between bone resorption and formation by osteoclasts and osteoblasts, respectively. An imbalance between osteoblasts and osteoclasts increases the risk of osteoporosis and fractures. Although inhibition of osteoclasts is beneficial for preventing and treating osteoporosis, enhanced bone formation through activation of osteoblast differentiation can be a more promising therapeutic approach. In this study, we attempted to isolate small molecules that promote osteoblast differentiation and found that IBIP (3-(2,3-dimethoxyphenyl)-1-[9-methyl-2-phenyl-9H-imidazo[1,2-a]benzimidazol-3-yl]-2-propen-1-one) was a potent activator of osteoblast differentiation. Upon bone morphogenetic protein-2 (BMP2) stimulation, IBIP promoted osteoblast differentiation and increased the expression of osteoblast-specific gene markers, such as osterix and alkaline phosphatase, in a dose-dependent manner. The phosphorylation of SMADs and extracellular signal-regulated kinase (ERK) increased after IBIP treatment. While enhanced SMAD phosphorylation by IBIP was abolished by a BMP inhibitor, IBIP-induced ERK phosphorylation was sustained in the presence of this inhibitor, but was decreased by an ERK kinase inhibitor. Suppression of IBIP-induced SMAD and ERK phosphorylation diminished osteoblast differentiation. Most importantly, IBIP enhanced bone formation and calcification in a BMP2-independent manner in vitro and advanced the skeletal development of zebrafish larvae in vivo. Collectively, IBIP may have beneficial effects on bone loss through potentiation of bone formation.

Original languageEnglish
Pages (from-to)409-414
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - 27 May 2017

Bibliographical note

Funding Information:
We thank Dr. Hyun-Mo Ryoo (Seoul National University) for providing 6xOSE2-luc and Dr. Myung Ae Bae (KRICT) for sharing the zebrafish facility. This work was supported by Mid-career research program of the National Research Foundation (ESH, NRF-2016R1D1A1B03935951) funded by the Ministry of Education, Science, and Technology.

Publisher Copyright:
© 2017 Elsevier Inc.


  • BMP2
  • ERK
  • IBIP
  • Osteoblast differentiation
  • SMAD


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