Computational Optimization Of Purmorphamine-Derived Small Molecule Modulators Targeting The Secretin Receptor (SCTR) For Antihypertensive Therapy
DOI:
https://doi.org/10.62051/ggrvpv67Keywords:
Hypertension; secretin receptor (SCTR); structure-based drug design.Abstract
Hypertension remains a global health problem. Although existing treatments (such as ACE inhibitors, β-blockers, etc.) are widely available, their side effects and patient compliance issues limit the therapeutic effect. Therefore, the development of new small molecule drugs is particularly important. This study targets pancreatic cholinergic receptors (SCTR), which play an important role in vasodilation and blood pressure regulation and have the potential to become a new target for antihypertensive drugs. In this study, based on the small molecule compound puromorphamine, the structure was optimized by computer-aided drug design method, combined with ADMET prediction and structure-activity relationship analysis (SAR), and the candidate compound KSD179019 was obtained. The results of virtual screening and molecular docking showed that the optimized molecule had good receptor binding ability and pharmacokinetic properties, reflecting its application prospects as a potential antihypertensive drug. Although no in vitro or in vivo experiments have been conducted, this study provides a theoretical basis for subsequent experimental verification and also demonstrates the great potential of artificial intelligence technology in new drug research and development, especially in the acceleration of G protein-coupled receptor (GPCR) target drug development.
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