1v7a: Difference between revisions

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[[Image:1v7a.jpg|left|200px]]<br /><applet load="1v7a" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1v7a.jpg|left|200px]]<br /><applet load="1v7a" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1v7a, resolution 2.5Å" />

'''Crystal structures of adenosine deaminase complexed with potent inhibitors'''<br />

==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.

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==

1V7A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ZN and FRC as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1V7A OCA].

1V7A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=FRC:'>FRC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V7A OCA].

==Reference==

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[[Category: zinc]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 04:29:~~34 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:32:14 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1v7a.jpg|left|200px]]<br /><applet load="1v7a" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1v7a.jpg|left|200px]]<br /><applet load="1v7a" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1v7a, resolution 2.5&Aring;" />
 '''Crystal structures of adenosine deaminase complexed with potent inhibitors'''<br />
 ==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.
+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==
-V7A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ZN and FRC as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1V7A OCA].
+V7A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=FRC:'>FRC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V7A OCA].
 ==Reference==
@@ Line 20: / Line 20: @@
 [[Category: zinc]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 04:29:34 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:32:14 2008''