Discovery and preclinical profile of ALG-055009, a potent and selective thyroid hormone receptor beta (THR-&lt;em&gt;β&lt;/em&gt;) agonist for the treatment of MASH

Vandyck, Koen; McGowan, David C.; Luong, Xuan G.; Stevens, Sarah K.; Jekle, Andreas; Gupta, Kusum; Misner, Dinah L.; Chanda, Sushmita; Serebryany, Vladimir; Welch, Michael; Hu, Haiyang; Lv, Zhidan; Williams, Caroline; Maskos, Klaus; Lammens, Alfred; Stoycheva, Antitsa D.; Lin, Tse I.; Blatt, Lawrence M.; Beigelman, Leonid N.; Symons, Julian A.; Raboisson, Pierre; Deval, Jerome

doi:10.1021/acs.jmedchem.4c01029

Discovery and preclinical profile of ALG-055009, a potent and selective thyroid hormone receptor beta (THR-β) agonist for the treatment of MASH

Vandyck K, McGowan DC, Luong XG, Stevens SK, Jekle A, Gupta K, Misner DL, Chanda S, Serebryany V, Welch M, Hu H, Lv Z, Williams C, Maskos K, Lammens A, Stoycheva AD, Lin TI, Blatt LM, Beigelman LN, Symons JA, Raboisson P & Deval J

Citation

Vandyck, K., McGowan, D. C., Luong, X. G., Stevens, S. K., Jekle, A., Gupta, K., … Deval, J. (2024). Discovery and preclinical profile of ALG-055009, a potent and selective thyroid hormone receptor beta (THR-β) agonist for the treatment of MASH. Journal of Medicinal Chemistry, 67, 14840-14851. https://doi.org/10.1021/acs.jmedchem.4c01029

Persistent URL https://www.dora.lib4ri.ch/psi/islandora/object/psi:66126

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 (14) 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.

Details

Publication Type

Journal Article

Title

Discovery and preclinical profile of ALG-055009, a potent and selective thyroid hormone receptor beta (THR-β) agonist for the treatment of MASH

Author(s)

Vandyck, Koen

McGowan, David C.

Luong, Xuan G.

Stevens, Sarah K.

Jekle, Andreas

Gupta, Kusum

Misner, Dinah L.

Chanda, Sushmita

Serebryany, Vladimir

Welch, Michael

Hu, Haiyang

Lv, Zhidan

Williams, Caroline

Maskos, Klaus

Lammens, Alfred

Stoycheva, Antitsa D.

Lin, Tse I.

Blatt, Lawrence M.

Beigelman, Leonid N.

Symons, Julian A.

Raboisson, Pierre

Deval, Jerome

Journal

Journal of Medicinal Chemistry

Volume

Start Page

14840

End Page

14851

Publication Year

2024

Peer Review

Yes

Facility

SLS

Beamline

PX
PXII

Collection

External Publications