3FAA

Crystal structure of TGFbRI complexed with a 2-aminoimidazole inhibitor

Summary for 3FAA

• Entry DOI: 10.2210/pdb3faa/pdb
• Descriptor: TGF-beta receptor type-1, N-[4-(5-fluoro-6-methylpyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-yl]acetamide, PHOSPHATE ION (3 entities in total)
• Functional Keywords: kinase, tgfbeta, structure-based drug design, protein-inhibitor complex, atp-binding, craniosynostosis, disease mutation, glycoprotein, magnesium, manganese, membrane, metal-binding, nucleotide-binding, phosphoprotein, polymorphism, receptor, serine/threonine-protein kinase, transferase, transmembrane
• Biological source: Homo sapiens
• Cellular location: Cell membrane ; Single-pass type I membrane protein : P36897
• Total number of polymer chains: 5
• Total formula weight: 197649.63

Authors

Boriack-Sjodin, P.A.,Fitch, C. (deposition date: 2008-11-16, release date: 2009-01-27, Last modification date: 2023-12-27)

Primary citation

Bonafoux, D.,Chuaqui, C.,Boriack-Sjodin, P.A.,Fitch, C.,Hankins, G.,Josiah, S.,Black, C.,Hetu, G.,Ling, L.,Lee, W.C.
2-Aminoimidazoles inhibitors of TGF-beta receptor 1.
Bioorg.Med.Chem.Lett., 19:912-916, 2009

PubMed Abstract: The 4-(5-fluoro-6-methyl-pyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-ylamine 3 is a potent and selective inhibitor of TGF-betaR1. Substitution of the amino group of 3 typically led to a slight decrease in the affinity for the receptor and in TGF-beta-inducted PAI-luciferase reporter activity. However, 2-acetamidoimidazoles were identified as attractive candidates for further optimization as a result of their significant activity combined to their superior pharmacokinetic profile.

PubMed: 19135364
DOI: 10.1016/j.bmcl.2008.11.119

Experimental method

X-RAY DIFFRACTION (3.35 Å)