4U44

MAP4K4 in complex with inhibitor (compound 16)

Summary for 4U44

• Entry DOI: 10.2210/pdb4u44/pdb
• Related: 4U3Y 4U3Z 4U40 4U41 4U42 4U43 4U45
• Descriptor: Mitogen-activated protein kinase kinase kinase kinase 4, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, SODIUM ION, ... (5 entities in total)
• Functional Keywords: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : O95819
• Total number of polymer chains: 2
• Total formula weight: 76245.70

Authors

Harris, S.F.,Wu, P.,Coons, M. (deposition date: 2014-07-23, release date: 2014-09-03, Last modification date: 2023-12-27)

Primary citation

Wang, L.,Stanley, M.,Boggs, J.W.,Crawford, T.D.,Bravo, B.J.,Giannetti, A.M.,Harris, S.F.,Magnuson, S.R.,Nonomiya, J.,Schmidt, S.,Wu, P.,Ye, W.,Gould, S.E.,Murray, L.J.,Ndubaku, C.O.,Chen, H.
Fragment-based identification and optimization of a class of potent pyrrolo[2,1-f][1,2,4]triazine MAP4K4 inhibitors.
Bioorg.Med.Chem.Lett., 24:4546-4552, 2014

PubMed Abstract: MAP4K4 has been shown to regulate key cellular processes that are tied to disease pathogenesis. In an effort to generate small molecule MAP4K4 inhibitors, a fragment-based screen was carried out and a pyrrolotriazine fragment with excellent ligand efficiency was identified. Further modification of this fragment guided by X-ray crystal structures and molecular modeling led to the discovery of a series of promising compounds with good structural diversity and physicochemical properties. These compounds exhibited single digit nanomolar potency and compounds 35 and 44 achieved good in vivo exposure.

PubMed: 25139565
DOI: 10.1016/j.bmcl.2014.07.071

Experimental method

X-RAY DIFFRACTION (2.43 Å)