3hc8

Investigation of Aminopyridiopyrazinones as PDE5 Inhibitors: Evaluation of Modifications to the Central Ring System.Investigation of Aminopyridiopyrazinones as PDE5 Inhibitors: Evaluation of Modifications to the Central Ring System.

Structural highlights

3hc8 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.79Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PDE5A_HUMAN Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.PDE4A_HUMAN Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Efforts to improve the potency and physical properties of the aminopyridiopyrazinone class of PDE5 inhibitors through modification of the core ring system are described. Five new ring systems are evaluated and features that impart improved potency and improved solubility are delineated.

Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system.,Hughes RO, Walker JK, Cubbage JW, Fobian YM, Rogier DJ, Heasley SE, Blevis-Bal RM, Benson AG, Owen DR, Jacobsen EJ, Freskos JN, Molyneaux JM, Brown DL, Stallings WC, Acker BA, Maddux TM, Tollefson MB, Williams JM, Moon JB, Mischke BV, Rumsey JM, Zheng Y, Macinnes A, Bond BR, Yu Y Bioorg Med Chem Lett. 2009 Aug 1;19(15):4092-6. Epub 2009 Jun 6. PMID:19539468^[3]

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

References

↑ Lario PI, Bobechko B, Bateman K, Kelly J, Vrielink A, Huang Z. Purification and characterization of the human PDE4A catalytic domain (PDE4A330-723) expressed in Sf9 cells. Arch Biochem Biophys. 2001 Oct 1;394(1):54-60. PMID:11566027 doi:http://dx.doi.org/10.1006/abbi.2001.2513
↑ Wang H, Peng MS, Chen Y, Geng J, Robinson H, Houslay MD, Cai J, Ke H. Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors. Biochem J. 2007 Dec 1;408(2):193-201. PMID:17727341 doi:http://dx.doi.org/10.1042/BJ20070970
↑ Hughes RO, Walker JK, Cubbage JW, Fobian YM, Rogier DJ, Heasley SE, Blevis-Bal RM, Benson AG, Owen DR, Jacobsen EJ, Freskos JN, Molyneaux JM, Brown DL, Stallings WC, Acker BA, Maddux TM, Tollefson MB, Williams JM, Moon JB, Mischke BV, Rumsey JM, Zheng Y, Macinnes A, Bond BR, Yu Y. Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4092-6. Epub 2009 Jun 6. PMID:19539468 doi:10.1016/j.bmcl.2009.06.004

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OCA

[1] Lario PI, Bobechko B, Bateman K, Kelly J, Vrielink A, Huang Z. Purification and characterization of the human PDE4A catalytic domain (PDE4A330-723) expressed in Sf9 cells. Arch Biochem Biophys. 2001 Oct 1;394(1):54-60. PMID:11566027 doi:http://dx.doi.org/10.1006/abbi.2001.2513

[2] Wang H, Peng MS, Chen Y, Geng J, Robinson H, Houslay MD, Cai J, Ke H. Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors. Biochem J. 2007 Dec 1;408(2):193-201. PMID:17727341 doi:http://dx.doi.org/10.1042/BJ20070970

[3] Hughes RO, Walker JK, Cubbage JW, Fobian YM, Rogier DJ, Heasley SE, Blevis-Bal RM, Benson AG, Owen DR, Jacobsen EJ, Freskos JN, Molyneaux JM, Brown DL, Stallings WC, Acker BA, Maddux TM, Tollefson MB, Williams JM, Moon JB, Mischke BV, Rumsey JM, Zheng Y, Macinnes A, Bond BR, Yu Y. Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4092-6. Epub 2009 Jun 6. PMID:19539468 doi:10.1016/j.bmcl.2009.06.004

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