4L52

Crystal Structure of 1-(4-{4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethan-1-one bound to TAK1-TAB1

Summary for 4L52

• Entry DOI: 10.2210/pdb4l52/pdb
• Related: 4L3P 4L53
• Descriptor: Mitogen-activated protein kinase kinase kinase 7, TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 chimera, 1-(4-{4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone (3 entities in total)
• Functional Keywords: tak1 kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 35168.57

Authors

Wang, J.,Hornberger, K.R.,Crew, A.P.,Jestel, A.,Maskos, K.,Moertl, M. (deposition date: 2013-06-10, release date: 2013-07-03, Last modification date: 2024-10-30)

Primary citation

Hornberger, K.R.,Berger, D.M.,Crew, A.P.,Dong, H.,Kleinberg, A.,Li, A.H.,Medeiros, M.R.,Mulvihill, M.J.,Siu, K.,Tarrant, J.,Wang, J.,Weng, F.,Wilde, V.L.,Albertella, M.,Bittner, M.,Cooke, A.,Gray, M.J.,Maresca, P.,May, E.,Meyn, P.,Peick, W.,Romashko, D.,Tanowitz, M.,Tokar, B.
Discovery and optimization of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1.
Bioorg.Med.Chem.Lett., 23:4517-4522, 2013

PubMed Abstract: The discovery and potency optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. Micromolar hits taken from high-throughput screening were optimized for biochemical and cellular mechanistic potency to ~10nM, as exemplified by compound 12az. Application of structure-based drug design aided by co-crystal structures of TAK1 with inhibitors significantly shortened the number of iterations required for the optimization.

PubMed: 23850198
DOI: 10.1016/j.bmcl.2013.06.053

Experimental method

X-RAY DIFFRACTION (2.54 Å)