2WOT

ALK5 IN COMPLEX WITH 4-((5,6-dimethyl-2-(2-pyridyl)-3-pyridyl)oxy)-N-(3,4,5-trimethoxyphenyl)pyridin-2-amine

Summary for 2WOT

• Entry DOI: 10.2210/pdb2wot/pdb
• Related: 1B6C 1IAS 1PY5 1RW8 1VJY 2WOU
• Descriptor: TGF-BETA RECEPTOR TYPE-1, 4-[(5,6-DIMETHYL-2,2'-BIPYRIDIN-3-YL)OXY]-N-(3,4,5-TRIMETHOXYPHENYL)PYRIDIN-2-AMINE, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: alk5, kinase, membrane, receptor, manganese, serine/threonine-protein kinase, kinase inhibitor, disease mutation, craniosynostosis, nucleotide-binding, tgf beta type i receptor, phosphoprotein, disulfide bond, aortic aneurysm, glycoprotein, metal-binding, transmembrane, atp-binding, transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 35459.78

Authors

Norman, R.A.,Debreczeni, J.E.,Goldberg, F.W.,Ward, R.A.,Finlay, R.,Powell, S.J.,Roberts, N.J.,Dishington, A.P.,Gingell, H.J.,Wickson, K.F.,Roberts, A.L. (deposition date: 2009-07-28, release date: 2009-09-22, Last modification date: 2024-05-08)

Primary citation

Goldberg, F.W.,Ward, R.A.,Powell, S.J.,Debreczeni, J.E.,Norman, R.A.,Roberts, N.J.,Dishington, A.P.,Gingell, H.J.,Wickson, K.F.,Roberts, A.L.
Rapid Generation of a High Quality Lead for Transforming Growth Factor-Beta (Tgf-Beta) Type I Receptor (Alk5).
J.Med.Chem., 52:7901-, 2009

PubMed Abstract: A novel class of 4-pyridinoxy-2-anilinopyridine-based TGF-beta type I receptor (also known as activin-like kinase 5 or ALK5) inhibitors is reported. The binding mode of this scaffold was successfully predicted by analyzing possible docked binding modes of literature inhibitors and novel synthetic ideas. Compounds such as 19 are potent ALK5 inhibitors with good physicochemical and pharmacokinetic properties and thus represent high quality leads for further optimization.

PubMed: 19736928
DOI: 10.1021/JM900807W

Experimental method

X-RAY DIFFRACTION (1.85 Å)