Structural highlights
5w6e 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.
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| Ligands: | , , |
| Gene: | PDE1B, PDE1B1, PDES1B (HUMAN) |
| Activity: | 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[PDE1B_HUMAN] Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a preference for cGMP as a substrate.
Publication Abstract from PubMed
We disclose the discovery and X-ray cocrystal data of potent, selective quinazoline inhibitors of PDE1. Inhibitor ( S)-3 readily attains free plasma concentrations above PDE1 IC50 values and has restricted brain access. The racemic compound 3 inhibits >75% of PDE hydrolytic activity in soluble samples of human myocardium, consistent with heightened PDE1 activity in this tissue. These compounds represent promising new tools to probe the value of PDE1 inhibition in the treatment of cardiovascular disease.
Discovery of Potent and Selective Periphery-Restricted Quinazoline Inhibitors of the Cyclic Nucleotide Phosphodiesterase PDE1.,Humphrey JM, Movsesian M, Am Ende CW, Becker SL, Chappie TA, Jenkinson S, Liras JL, Liras S, Orozco C, Pandit J, Vajdos FF, Vandeput F, Yang E, Menniti FS J Med Chem. 2018 May 24;61(10):4635-4640. doi: 10.1021/acs.jmedchem.8b00374. Epub, 2018 May 10. PMID:29718668[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Humphrey JM, Movsesian M, Am Ende CW, Becker SL, Chappie TA, Jenkinson S, Liras JL, Liras S, Orozco C, Pandit J, Vajdos FF, Vandeput F, Yang E, Menniti FS. Discovery of Potent and Selective Periphery-Restricted Quinazoline Inhibitors of the Cyclic Nucleotide Phosphodiesterase PDE1. J Med Chem. 2018 May 24;61(10):4635-4640. doi: 10.1021/acs.jmedchem.8b00374. Epub, 2018 May 10. PMID:29718668 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b00374
