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4pm0

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Revision as of 12:02, 6 November 2017

PDE7A catalytic domain in complex with 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivative

Structural highlights

4pm0 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	PDE7A (HUMAN)
Activity:	3',5'-cyclic-AMP phosphodiesterase, with EC number 3.1.4.53
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PDE7A_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction.^[1]

Publication Abstract from PubMed

The discovery of a new series of potent phosphodiesterase 7 (PDE7) inhibitors is described. Novel thieno[3,2-d]pyrimidin-4(3H)-one hit compounds were identified from our chemical library. Preliminary modifications of the hit compounds were performed, resulting in the discovery of a fragment-sized compound (10) with highly improved ligand efficiency. Compound design was guided by structure-activity relationships and computational modeling. The 6-substituted derivatives of the thienopyrimidinone showed diminished activity and enzyme selectivity. However, synthesis of the 7-substituted derivatives resulted in the discovery of 28e, a desirable lead compound that selectively inhibits PDE7 with single-digit nanomolar potency while displaying potent cellular efficacy.

Discovery of 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one Derivatives as a New Series of Potent Phosphodiesterase 7 Inhibitors.,Kawai K, Endo Y, Asano T, Amano S, Sawada K, Ueo N, Takahashi N, Sonoda Y, Nagai M, Kamei N, Nagata N J Med Chem. 2014 Nov 19. PMID:25383422^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Castano T, Wang H, Campillo NE, Ballester S, Gonzalez-Garcia C, Hernandez J, Perez C, Cuenca J, Perez-Castillo A, Martinez A, Huertas O, Gelpi JL, Luque FJ, Ke H, Gil C. Synthesis, Structural Analysis, and Biological Evaluation of Thioxoquinazoline Derivatives as Phosphodiesterase 7 Inhibitors. ChemMedChem. 2009 Apr 6. PMID:19350606 doi:10.1002/cmdc.200900043
↑ Kawai K, Endo Y, Asano T, Amano S, Sawada K, Ueo N, Takahashi N, Sonoda Y, Nagai M, Kamei N, Nagata N. Discovery of 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one Derivatives as a New Series of Potent Phosphodiesterase 7 Inhibitors. J Med Chem. 2014 Nov 19. PMID:25383422 doi:http://dx.doi.org/10.1021/jm5008215

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4pm0"

@@ Line 3: / Line 3: @@
 <StructureSection load='4pm0' size='340' side='right' caption='[[4pm0]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4pm0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PM0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4pm0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PM0 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=32V:2-(CYCLOPENTYLAMINO)-3-ETHYL-7-ETHYNYLTHIENO[3,2-D]PYRIMIDIN-4(3H)-ONE'>32V</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE7A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-AMP_phosphodiesterase 3',5'-cyclic-AMP phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.53 3.1.4.53] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pm0 OCA], [http://pdbe.org/4pm0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pm0 RCSB], [http://www.ebi.ac.uk/pdbsum/4pm0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pm0 ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 </StructureSection>
 [[Category: 3',5'-cyclic-AMP phosphodiesterase]]
+[[Category: Human]]
 [[Category: Amano, S]]
 [[Category: Asano, T]]

4pm0

From Proteopedia

Revision as of 12:02, 6 November 2017

PDE7A catalytic domain in complex with 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivative

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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