| Structural highlights
6acb 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: | PDE5A, PDE5 (HUMAN) |
| Activity: | 3',5'-cyclic-GMP phosphodiesterase, with EC number 3.1.4.35 |
| 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.
Publication Abstract from PubMed
To further explore the structure-activity relationship around the chromeno[2,3- c]pyrrol-9(2 H)-one scaffold, 19 derivatives as inhibitors against PDE5 were discovered. The most potent inhibitor 3 has an IC50 of 0.32 nM with remarkable selectivity and druglike profile. Oral administration of 3 (1.25 mg/kg) caused comparable therapeutic effects to sildenafil (10.0 mg/kg) against pulmonary arterial hypertension. Further, different binding patterns from sildenafil were revealed in cocrystal structures, which provide structural templates for discovery of highly potent PDE5 inhibitors.
Optimization of Chromeno[2,3- c]pyrrol-9(2 H)-ones as Highly Potent, Selective, and Orally Bioavailable PDE5 Inhibitors: Structure-Activity Relationship, X-ray Crystal Structure, and Pharmacodynamic Effect on Pulmonary Arterial Hypertension.,Wu D, Huang Y, Chen Y, Huang YY, Geng H, Zhang T, Zhang C, Li Z, Guo L, Chen J, Luo HB J Med Chem. 2018 Sep 7. doi: 10.1021/acs.jmedchem.8b01209. PMID:30148362[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wu D, Huang Y, Chen Y, Huang YY, Geng H, Zhang T, Zhang C, Li Z, Guo L, Chen J, Luo HB. Optimization of Chromeno[2,3- c]pyrrol-9(2 H)-ones as Highly Potent, Selective, and Orally Bioavailable PDE5 Inhibitors: Structure-Activity Relationship, X-ray Crystal Structure, and Pharmacodynamic Effect on Pulmonary Arterial Hypertension. J Med Chem. 2018 Sep 7. doi: 10.1021/acs.jmedchem.8b01209. PMID:30148362 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b01209
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