4G2W
Crystal structure of PDE5A in complex with its inhibitor
Summary for 4G2W
| Entry DOI | 10.2210/pdb4g2w/pdb |
| Related | 4G2Y |
| Descriptor | cGMP-specific 3',5'-cyclic phosphodiesterase, 5,6-diethyl-2-{5-[(4-methylpiperazin-1-yl)sulfonyl]-2-propoxyphenyl}pyrimidin-4(3H)-one, MAGNESIUM ION, ... (6 entities in total) |
| Functional Keywords | phosphodiesterase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 40735.50 |
| Authors | Ren, J.,Chen, T.T.,Xu, Y.C. (deposition date: 2012-07-13, release date: 2013-06-26, Last modification date: 2023-11-08) |
| Primary citation | Wang, G.,Liu, Z.,Chen, T.T.,Wang, Z.,Yang, H.,Zheng, M.,Ren, J.,Tian, G.,Yang, X.,Li, L.,Li, J.,Suo, J.,Zhang, R.,Jiang, X.,Terrett, N.K.,Shen, J.,Xu, Y.C.,Jiang, H. Design, synthesis, and pharmacological evaluation of monocyclic pyrimidinones as novel inhibitors of PDE5. J.Med.Chem., 55:10540-10550, 2012 Cited by PubMed Abstract: Cyclic nucleotide phosphodiesterase type 5 (PDE5) is a prime drug target for treating the diseases associated with a lower level of the cyclic guanosine monophosphate (cGMP), which is a specific substrate for PDE5 hydrolysis. Here we report a series of novel PDE5 inhibitors with the new scaffold of the monocyclic pyrimidin-4(3H)-one ring developed using the structure-based discovery strategy. In total, 37 derivatives of the pyrimidin-4(3H)-ones, were designed, synthesized, and evaluated for their inhibitory activities to PDE5, resulting in 25 compounds with IC50 ranging from 1 to 100 nM and 11 compounds with IC50 ranging from 1 to 10 nM. Compound 5, 5,6-diethyl-2-[2-n-propoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]pyrimid-4(3H)-one, the most potent compound, has an excellent IC50 (1.6 nM) in vitro and a good efficacy in a rat model of erection. It thus provides a potential candidate for the further development into a new drug targeting PDE5. PubMed: 23137303DOI: 10.1021/jm301159y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.28 Å) |
Structure validation
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