3GXL

ALK-5 kinase complex with GW857175

Summary for 3GXL

• Entry DOI: 10.2210/pdb3gxl/pdb
• Related: 3GXJ
• Descriptor: TGF-beta receptor type-1, N-1H-indazol-5-yl-2-(6-methylpyridin-2-yl)quinazolin-4-amine (3 entities in total)
• Functional Keywords: tgf-beta, alk5, kinase, inhibitor, quinazoline, aortic aneurysm, atp-binding, craniosynostosis, disease mutation, disulfide bond, glycoprotein, magnesium, manganese, membrane, metal-binding, nucleotide-binding, phosphoprotein, polymorphism, receptor, serine/threonine-protein kinase, transferase, transmembrane
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane ; Single-pass type I membrane protein : P36897
• Total number of polymer chains: 1
• Total formula weight: 35076.38

Authors

Smith, W.,Janson, C. (deposition date: 2009-04-02, release date: 2009-04-21, Last modification date: 2023-11-01)

Primary citation

Gellibert, F.,Fouchet, M.-H.,Nguyen, V.-L.,Wang, R.,Krysa, G.,de Gouville, A.-C.,Huet, S.,Dodic, N.
Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors
Bioorg.Med.Chem.Lett., 19:2277-2281, 2009

PubMed Abstract: Starting from quinazoline 3a, we designed potent and selective ALK5 inhibitors over p38MAP kinase from a rational drug design approach based on co-crystal structures in the human ALK5 kinase domain. The quinazoline 3d exhibited also in vivo activity in an acute rat model of DMN-induced liver fibrosis when administered orally at 5mg/kg (bid).

PubMed: 19285388
DOI: 10.1016/j.bmcl.2009.02.087

Experimental method

X-RAY DIFFRACTION (1.8 Å)