2EA2

h-MetAP2 complexed with A773812

Summary for 2EA2

• Entry DOI: 10.2210/pdb2ea2/pdb
• Related: 1YW7 1YW8 1YW9 2EA4 2GA2
• Descriptor: Methionine aminopeptidase 2, MANGANESE (II) ION, 3-ETHYL-6-{[(4-FLUOROPHENYL)SULFONYL]AMINO}-2-METHYLBENZOIC ACID, ... (4 entities in total)
• Functional Keywords: protein-ligand complex, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 41817.25

Authors

Park, C.H. (deposition date: 2007-01-30, release date: 2008-02-05, Last modification date: 2024-10-23)

Primary citation

Wang, G.T.,Mantei, R.A.,Kawai, M.,Tedrow, J.S.,Barnes, D.M.,Wang, J.,Zhang, Q.,Lou, P.,Garcia, L.A.,Bouska, J.,Yates, M.,Park, C.,Judge, R.A.,Lesniewski, R.,Sheppard, G.S.,Bell, R.L.
Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids
Bioorg.Med.Chem.Lett., 17:2817-2822, 2007

PubMed Abstract: A series of aryl sulfonamides of 5,6-disubstituted anthranilic acids were identified as potent inhibitors of methionine aminopeptidase-2 (MetAP2). Small alkyl groups and 3-furyl were tolerated at the 5-position of anthranilic acid, while -OCH(3), CH(3), and Cl were found optimal for the 6-position. Placement of 2-aminoethoxy group at the 6-position enabled interaction with the second Mn(2+) but did not result in enhancement in potency. Introduction of a tertiary amino moiety at the ortho-position of the sulfonyl phenyl ring gave reduced protein binding and improved cellular activity, but led to lower oral bioavailability.

PubMed: 17350258
DOI: 10.1016/j.bmcl.2007.02.062

Experimental method

X-RAY DIFFRACTION (2.5 Å)