1v79

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Revision as of 02:22, 21 November 2007

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spinqualitylabelsall models 1v79, resolution 2.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structures of adenosine deaminase complexed with potent inhibitors

Overview

We disclose optimization efforts based on the novel non-nucleoside, adenosine deaminase (ADA) inhibitor, 4 (K(i) = 680 nM). Structure-based, drug design utilizing the crystal structure of the 4/ADA complex led to, discovery of 5 (K(i) = 11 nM, BA = 30% in rats). Furthermore, from, metabolic considerations, we discovered two inhibitors with improved oral, bioavailability [6 (K(i) = 13 nM, BA = 44%) and 7 (K(i) = 9.8 nM, BA =, 42%)]. 6 demonstrated in vivo efficacy in models of inflammation and, lymphoma.

About this Structure

1V79 is a Single protein structure of sequence from Bos taurus with ZN and FR7 as ligands. Active as Adenosine deaminase, with EC number 3.5.4.4 Full crystallographic information is available from OCA.

Reference

Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors., Terasaka T, Okumura H, Tsuji K, Kato T, Nakanishi I, Kinoshita T, Kato Y, Kuno M, Seki N, Naoe Y, Inoue T, Tanaka K, Nakamura K, J Med Chem. 2004 May 20;47(11):2728-31. PMID:15139750

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