Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 20, Issue 2, Pages 145-149Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14728222.2016.1090429
Keywords
cholesterol lowering; thyroid hormone receptors; eprotirome; sobetirome; KB2115; thyroid hormone; thyromimetic; GC-1; obesity; dyslipidemia
Categories
Funding
- NIDDK NIH HHS [RC4 DK090849] Funding Source: Medline
Ask authors/readers for more resources
Sobetirome binds selectively to the main hepatic form of thyroid hormone (TH) receptor, TR beta 1, compared to TR alpha 1, 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available