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Computational and Pharmacogenomic Insights on Hypertension Treatment: Rational Drug Design and Optimization Strategies.

Authors
  • Loganathan, Lakshmanan1, 2
  • Gopinath, Krishnasamy2
  • Sankaranarayanan, Vadivel Murugan3
  • Kukreti, Ritushree4
  • Rajendran, Kannan5
  • Lee, Jung-Kul2
  • Muthusamy, Karthikeyan1
  • 1 Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, India. , (India)
  • 2 Department of Chemical Engineering, Konkuk University, 1 Hwayang-Dong, Gwangjin-Gu, Seoul, Korea. , (North Korea)
  • 3 Department of General Medicine, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu, India. , (India)
  • 4 Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research, New Delhi, India. , (India)
  • 5 Department of General Medicine, Saveetha Medical College and Hospital, Chennai, Tamil Nadu, India. , (India)
Type
Published Article
Journal
Current drug targets
Publication Date
Jan 01, 2020
Volume
21
Issue
1
Pages
18–33
Identifiers
DOI: 10.2174/1389450120666190808101356
PMID: 31393243
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Hypertension is a prevalent cardiovascular complication caused by genetic and nongenetic factors. Blood pressure (BP) management is difficult because most patients become resistant to monotherapy soon after treatment initiation. Although many antihypertensive drugs are available, some patients do not respond to multiple drugs. Identification of personalized antihypertensive treatments is a key for better BP management. This review aimed to elucidate aspects of rational drug design and other methods to develop better hypertension management. Among hypertension-related signaling mechanisms, the renin-angiotensin-aldosterone system is the leading genetic target for hypertension treatment. Identifying a single drug that acts on multiple targets is an emerging strategy for hypertension treatment, and could be achieved by discovering new drug targets with less mutated and highly conserved regions. Extending pharmacogenomics research to include patients with hypertension receiving multiple antihypertensive drugs could help identify the genetic markers of hypertension. However, available evidence on the role of pharmacogenomics in hypertension is limited and primarily focused on candidate genes. Studies on hypertension pharmacogenomics aim to identify the genetic causes of response variations to antihypertensive drugs. Genetic association studies have identified single nucleotide polymorphisms affecting drug responses. To understand how genetic traits alter drug responses, computational screening of mutagenesis can be utilized to observe drug response variations at the protein level, which can help identify new inhibitors and drug targets to manage hypertension. Rational drug design facilitates the discovery and design of potent inhibitors. However, further research and clinical validation are required before novel inhibitors can be clinically used as antihypertensive therapies. Copyright© Bentham Science Publishers; For any queries, please email at [email protected]

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