Advantages
- Novel synthetic compound
- Higher THRβ selectivity
- Higher safety
Background and Technology
There are two subtypes of THR: α and β. The ligand TH is known to activate cholesterol metabolism in the liver and decrease blood lipid concentrations via THRβ, while binding to THRα causes adverse effects such as arrhythmia and loss of muscle and bone mass. Therefore, TH analogs that selectively bind to THRβ may be excellent therapeutic agents with fewer side effects for NASH, dyslipidemia, and obesity. Representative THRβ-selective TH analogs known so far include GC-1 (Sobetirome) and GC-24. In particular, the THRβ selectivity of GC-1 has been demonstrated in several animal models, and clinical trials as a novel cholesterol-lowering agent were conducted but discontinued due to toxicity issues.
We have successfully developed a novel TH analog compound with high affinity and selectivity for THRβ. The structure with enhanced hydrophobicity while maintaining a conformation favorable for binding to the receptor has resulted in high selectivity for THRβ in vitro and in vivo (bottom left). Oral administration of the compound to obese model mice with a high-fat diet showed an improvement in lipid metabolism (bottom right), and it showed no toxicity at high concentrations.
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Reference and Patent
- Academic paper under submission
- Patent pending
Principal Investigator
Takashi YOSHIMURA (Institute of Transformative Bio-Molecules, Nagoya University, Tokai National Higher Education and Research System)
Current Stage and Next Step
- Currently at the stage of designing and synthesizing a new compound and confirming basic drug efficacy and safety through in vitro and in vivo experiments at the laboratory level.
- In the future, we would like to conduct feasibility studies to evaluate the potential of this compound as a therapeutic drug and are looking for partner companies to collaborate with us.
Project No. BK-04471