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Heart Fail Rev. 2010 Mar;15(2):177-82. doi: 10.1007/s10741-008-9122-x. Epub 2008 Nov 11.

Sobetirome: a case history of bench-to-clinic drug discovery and development.

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Department of Physiology & Pharmacology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239-3098, USA.


Sobetirome, also known as GC-1 and QRX-431, is a member of a class of compounds known as selective thyromimetics (Scanlan et al., Curr Opin Drug Discov Dev 4:614-622). These compounds are synthetic structural analogs of thyroid hormone that have tissue-specific thyroid hormone actions. Many of the compounds in this class, including sobetirome, also are subtype-selective thyroid hormone receptor (TR) agonists. Sobetirome selectively binds to and activates TRbeta over TRalpha and this receptor selectivity led to the hypothesis that sobetirome would lower cholesterol through activation of liver TRbeta without stimulating cardiac function through TRalpha activation in the heart. The tissue selective thyromimetic properties of sobetirome have been demonstrated in numerous animal models, which led to its clinical development as a novel cholesterol-lowering agent. This review will describe the discovery and development journey of sobetirome as a case history.

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