ArticlePloS one2012
Design novel dual agonists for treating type-2 diabetes by targeting peroxisome proliferator-activated receptors with core hopping approach.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 109 citations in OpenAlex.
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- To Probe Full and Partial Activation of Human Peroxisome Proliferator-Activated Receptors by Pan-Agonist Chiglitazar Using Molecular Dynamics Simulations.PPAR research · 2020Article
- Current Biochemical Applications and Future Prospects of Chlorotoxin in Cancer Diagnostics and Therapeutics.Advanced pharmaceutical bulletin · 2019Review
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- RAACBook: a web server of reduced amino acid alphabet for sequence-dependent inference by using Chou's five-step rule.Database : the journal of biological databases and curation · 2019Article
- A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs.Molecules (Basel, Switzerland) · 2018Article
- Structural insights of dipeptidyl peptidase-IV inhibitors through molecular dynamics-guided receptor-dependent 4D-QSAR studies.Molecular diversity · 2018Article
- Small molecular floribundiquinone B derived from medicinal plants inhibits acetylcholinesterase activity.Oncotarget · 2017Article
- The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study.Oncotarget · 2017Article
- Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation.International journal of molecular sciences · 2016Article
- Role of peroxisome proliferator-activated receptors gene polymorphisms in type 2 diabetes and metabolic syndrome.World journal of diabetes · 2015Review
- Sequence-specific flexibility organization of splicing flanking sequence and prediction of splice sites in the human genome.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2014Article
- iNR-Drug: predicting the interaction of drugs with nuclear receptors in cellular networking.International journal of molecular sciences · 2014Article
- Identification of novel multitargeted PPARα/γ/δ pan agonists by core hopping of rosiglitazone.Drug design, development and therapy · 2014Article
- Bioassay directed isolation and biological evaluation of compounds isolated from Rubus fairholmianus Gard.BioMed research international · 2014Article
- Design, synthesis, biological activity and molecular dynamics studies of specific protein tyrosine phosphatase 1B inhibitors over SHP-2.International journal of molecular sciences · 2013Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Owing to their unique functions in regulating glucose, lipid and cholesterol metabolism, PPARs (peroxisome proliferator-activated receptors) have drawn special attention for developing drugs to treat type-2 diabetes. By combining the lipid benefit of PPAR-alpha agonists (such as fibrates) with the glycemic advantages of the PPAR-gamma agonists (such as thiazolidinediones), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence has become a promising strategy for designing effective drugs against type-2 diabetes. In this study, by means of the powerful "core hopping" and "glide docking" techniques, a novel class of PPAR dual agonists was discovered based on the compound GW409544, a well-known dual agonist for both PPAR-alpha and PPAR-gamma modified from the farglitazar structure. It was observed by molecular dynamics simulations that these novel agonists not only possessed the same function as GW409544 did in activating PPAR-alpha and PPAR-gamma, but also had more favorable conformation for binding to the two receptors. It was further validated by the outcomes of their ADME (absorption, distribution, metabolism, and excretion) predictions that the new agonists hold high potential to become drug candidates. Or at the very least, the findings reported here may stimulate new strategy or provide useful insights for discovering more effective dual agonists for treating type-2 diabetes. Since the "core hopping" technique allows for rapidly screening novel cores to help overcome unwanted properties by generating new lead compounds with improved core properties, it has not escaped our notice that the current strategy along with the corresponding computational procedures can also be utilized to find novel and more effective drugs for treating other illnesses.
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