8RQO

Human thyroid hormone receptor alpha ligand binding domain in complex with beta-selective agonist ALG-055009

This is a non-PDB format compatible entry.

Summary for 8RQO

• Entry DOI: 10.2210/pdb8rqo/pdb
• Descriptor: Isoform Alpha-1 of Thyroid hormone receptor alpha, 6-azanyl-2-[3,5-bis(chloranyl)-4-[(6-oxidanylidene-5-propan-2-yl-1~{H}-pyridazin-3-yl)oxy]phenyl]-1,2,4-triazine-3,5-dione, SULFATE ION, ... (4 entities in total)
• Functional Keywords: thyroid receptor beta, thyroid receptor alpha, nuclear receptors, thyroid receptor agonist, thyroid receptor ligand, structure-based drug design, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 32772.39

Authors

Lammens, A.,Maskos, K.,Stoycheva, A.D.,McGowan, D.C. (deposition date: 2024-01-18, release date: 2024-09-11, Last modification date: 2024-09-25)

Primary citation

Vandyck, K.,McGowan, D.C.,Luong, X.G.,Stevens, S.K.,Jekle, A.,Gupta, K.,Misner, D.L.,Chanda, S.,Serebryany, V.,Welch, M.,Hu, H.,Lv, Z.,Williams, C.,Maskos, K.,Lammens, A.,Stoycheva, A.D.,Lin, T.I.,Blatt, L.M.,Beigelman, L.N.,Symons, J.A.,Raboisson, P.,Deval, J.
Discovery and Preclinical Profile of ALG-055009, a Potent and Selective Thyroid Hormone Receptor Beta (THR-beta ) Agonist for the Treatment of MASH.
J.Med.Chem., 67:14840-14851, 2024

PubMed Abstract: 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 () 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.

PubMed: 39221768
DOI: 10.1021/acs.jmedchem.4c01029

Experimental method

X-RAY DIFFRACTION (2.74 Å)