Sobetirome: a case history of bench-to-clinic drug discovery and development
- 11 November 2008
- journal article
- review article
- Published by Springer Science and Business Media LLC in Heart Failure Reviews
- Vol. 15 (2), 177-182
- https://doi.org/10.1007/s10741-008-9122-x
Abstract
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 TRβ over TRα and this receptor selectivity led to the hypothesis that sobetirome would lower cholesterol through activation of liver TRβ without stimulating cardiac function through TRα 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.Keywords
This publication has 30 references indexed in Scilit:
- The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humansProceedings of the National Academy of Sciences of the United States of America, 2008
- Targeting thyroid hormone receptor-β agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic indexProceedings of the National Academy of Sciences of the United States of America, 2007
- Thyroid hormone receptor β-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in ratsJournal of Endocrinology, 2007
- The Thyroid Hormone Receptor β-Specific Agonist GC-1 Selectively Affects the Bone Development of Hypothyroid RatsJournal of Bone and Mineral Research, 2005
- Induction of Larval Tissue Resorption in Xenopus laevis Tadpoles by the Thyroid Hormone Receptor Agonist GC-1Published by Elsevier BV ,2004
- Selective activation of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weightTrends in Endocrinology & Metabolism, 2004
- Structural Determinants of Selective ThyromimeticsJournal of Medicinal Chemistry, 2003
- A high-affinity subtype-selective agonist ligand for the thyroid hormone receptorCell Chemical Biology, 1998
- A structural role for hormone in the thyroid hormone receptorNature, 1995
- Synthesis and Structure-Activity Relationships of Oxamic Acid and Acetic Acid Derivatives Related to L-ThyronineJournal of Medicinal Chemistry, 1995