Discovery and Preclinical Profile of ALG-055009, a Potent and Selective Thyroid Hormone Receptor Beta (THR-β) Agonist for the Treatment of MASH
Agonists of thyroid hormone receptor β (THR-β) decreased LDL cholesterol (LDL-C) and triglyceride (TG) levels in human clinical trials for patients with dyslipidemia. The authors present the highly potent and selective compound ALG-055009 (<b>14</b>) as a potential best in class THR-β agonist. The high metabolic stability and good permeability translated well in vivo to afford a long in vivo half-life pharmacokinetic profile with limited liability for DDI, and it overcomes certain drawbacks seen in recent clinical candidates.
Authors
- Lawrence M. Blatt (ORCID: https://orcid.org/0000-0002-6442-9207)
- Tse‐I Lin
- Vladimir Serebryany
- Caroline Williams (ORCID: https://orcid.org/0000-0003-1783-5576)
- Antitsa Stoycheva (ORCID: https://orcid.org/0000-0003-1907-0319)
- Dinah Misner (ORCID: https://orcid.org/0000-0001-5054-678X)
- Sarah Stevens (ORCID: https://orcid.org/0000-0003-1461-2860)
- Alfred Lammens
- David C. McGowan (ORCID: https://orcid.org/0000-0002-3759-6771)
- Pierre Raboisson
- Andreas Jekle (ORCID: https://orcid.org/0000-0001-9416-2622)
- Hai Hu (ORCID: https://orcid.org/0000-0002-5348-5641)
- Sushmita Chanda
- K. Maskos
- Michael J. Welch (ORCID: https://orcid.org/0000-0001-7868-5079)
- Julian Symons
- Koen Vandyck (ORCID: https://orcid.org/0000-0002-0923-8301)
- Xuan G. Luong (ORCID: https://orcid.org/0000-0003-0600-8778)
- Jérôme Deval (ORCID: https://orcid.org/0000-0002-0133-4673)
- Leonid N. Beigelman
- Zhidan Lv
- Kusum Gupta
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2024-09-02
- DOI
- https://doi.org/10.1021/acs.jmedchem.4c01029
- Citations
- 32
- Primary Topic
- Neuroendocrine Tumor Research Advances
- Type
- article
- Field-Weighted Citation Impact
- 12.37