4u45 | pdb_00004u45

MAP4K4 in complex with inhibitor (compound 25)

spinqualitylabelsall models 4u45, resolution 2.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4u45 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 3DC, MES, MG Related: 4u3y, 4u3z, 4u40, 4u41, 4u42, 4u43, 4u44 Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [M4K4_HUMAN] Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322. Publication Abstract from PubMed 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. Fragment-based identification and optimization of a class of potent pyrrolo[2,1-f][1,2,4]triazine MAP4K4 inhibitors.,Wang L, Stanley M, Boggs JW, Crawford TD, Bravo BJ, Giannetti AM, Harris SF, Magnuson SR, Nonomiya J, Schmidt S, Wu P, Ye W, Gould SE, Murray LJ, Ndubaku CO, Chen H Bioorg Med Chem Lett. 2014 Aug 2. pii: S0960-894X(14)00795-1. doi:, 10.1016/j.bmcl.2014.07.071. PMID:25139565 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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