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Volume 21, Issue 16
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

PDE5 inhibitors have had a surge in popularity over the last decade owing to their efficacy in the treatment of erectile dysfunction, coronary vasculopathy, and pulmonary arterial hypertension. These inhibitors exhibit competitive binding with phosphodiesterase type 5 and inhibit the hydrolysis of cyclic guanosine monophosphate, hence elevating the levels of cGMP in smooth muscle cells and prolonging the duration of an erection. However, due to production costs and side effects, further research is needed to discover new PDE5 inhibitors.

Objectives

The study aimed to identify potent PDE5 inhibitors by employing the extensive application of computer-aided drug design.

Methods

Three different databases, named Million Molecules Database, Natural Product Database, and NCI Database, have been screened, which has been followed by filtering based on various drug-likeness rules, docking, ADME, toxicity, consensus molecular docking, and 100 ns molecular dynamics simulation.

Results

Three compounds (ZINC05351336, ZINC12030898, and ZINC17949426) have exhibited stable-binding characteristics at the active site of PDE5, demonstrating a robust binding affinity. These molecules have been found to possess drug-like capabilities, effective ADME features, low toxicity, and high stability.

Conclusion

The study has delved into the realm of PDE5 inhibitors, which have been found to be effective in treating erectile dysfunction, but high production costs and side effects necessitate new ones. Through computer-aided drug design and screening, three compounds have been identified with promising binding characteristics, drug-appropriate properties, effective ADME profiles, minimal toxicity, and stability, making them potential candidates for future PDE5 inhibitors.

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A Deep Dive into PDE5 Inhibition: Innovative Discoveries via Virtual Screening
Letters in Drug Design & Discovery 21, 3425 (2024); https://doi.org/10.2174/0115701808279586231221043744
/content/journals/lddd/10.2174/0115701808279586231221043744
/content/journals/lddd/10.2174/0115701808279586231221043744
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  • Article Type:     Research Article
Keyword(s): ADME profile; benign prostatic hyperplasia; erectile dysfunction; PDE5; PDE5 inhibitors; pulmonary arterial hypertension

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