Sobetirome: The past, present and questions about the future

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Abstract

Sobetirome binds selectively to the main hepatic form of thyroid hormone (TH) receptor, TRβ1, compared to TR1, which is principally responsible for thyrotoxic effects on heart, muscle and bone. Sobetirome also preferentially accumulates in liver. It was originally envisaged that sobetirome could be used to stimulate hepatic pathways that lower cholesterol without harmful side effects and might be used in conjunction with statins. Indeed, sobetirome progressed through preclinical animal studies and Phase I human clinical trials with excellent results and without obvious harmful side effects. Despite the fact that cardiovascular disease remains a major cause of mortality and that new therapies are desperately needed, it is unlikely that sobetirome will progress in further human clinical trials in the near future. The emergence of alternative cholesterol-lowering therapeutics may render selective thyromimetics redundant. Further, fears of thyrotoxic effects in the heart and emergence of cartilage defects in dogs after long-term use of eprotirome, a similar though not identical compound, has reduced enthusiasm for this strategy. We argue that it is nevertheless important to explore uses of sobetirome in humans; more treatment strategies would help patients with hard-to-treat dyslipidemias. Sobetirome may also have additional applications in orphan indications and short-term controlled weight loss.

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CITATION STYLE

APA

Lammel Lindemann, J., & Webb, P. (2016, February 1). Sobetirome: The past, present and questions about the future. Expert Opinion on Therapeutic Targets. Taylor and Francis Ltd. https://doi.org/10.1517/14728222.2016.1090429

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