Core Benefit
- Novel and multifaceted therapeutic strategy with the TAZ activator for muscle-wasting disorders.
Background and Technology
The transcriptional coactivator with a PDZ-binding motif (TAZ) cooperates with various transcriptional factors and plays various roles. Dr. Hata and colleagues developed a cell-based assay to screen 18,458 chemical compounds for TAZ activators. Finally, they focused on one compound, IBS008738, which increases the unphosphorylated TAZ level, enhances the association of MyoD with the myogenin promoter, upregulates MyoD-dependent gene transcription, and competes with myostatin in vitro. IBS008738 facilitates muscle repair in cardiotoxin-induced muscle injury and prevents dexamethasone-induced muscle atrophy in vivo. These findings also support the idea that TAZ is a potential therapeutic target for muscle atrophy.
Data
- (A) IBS008738facilitates the repair of cardiotoxin-injected muscles in vivovia promotion of satellite stem cell replication and differentiation into skeletal muscle lineage.
- (B) IBS008738 prevents dexamethasone-induced muscle atrophy in vivoby upregulation of protein synthesis and suppression of muscle-specific E3 ligases.
- IBS008738 competes with myostatin that inhibits muscle growth and differentiation.
- The malignant transformation of cancer cells with IBS008738 was not confirmed.
Publication
Zeyu Yang et. al. Molecular and Cellular Biology Vol.34 Num.9 p.1607–21
Patent
WO2015/119249 (PCT applied in Japanese)
Researcher
Dr. Yutaka Hata (Tokyo Medical Dental University, Japan)
Expectations
We are looking for a pharmaceutical company to collaborate with the researchers and develop this compound further under the patent licensing. IBS008738 and other TAZ activator could be provided for evaluation by MTA.
Product No. TP0411