Integrated in silico–in vitro screening of ovarian cancer peroxisome proliferator-activated receptor-γ agonists against a biogenic compound library

Zhang, Guilian; Liu, Fengying; Zhang, Jing; Wang, Liping; Jia, Erxia; Lv, Shi-Ming

doi:10.1007/s00044-017-2060-1

Cited by 3 publications

(4 citation statements)

References 34 publications

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“…PPARδ is the less studied receptor of this group ( 75 ) while PPARα and PPARγ have been extensively investigated as therapeutic targets especially in metabolic diseases like type 2 diabetes (T2D) ( 68 , 71 , 78 , 125 , 126 ). Recently, PPARγ has also been proposed as a therapeutic target for ovarian cancer ( 77 ) and Alzheimer Disease (AD) ( 78 ). In this review, 11 models and projects dedicated to PPARs have been identified.…”

Section: Studied Nuclear Receptorsmentioning

confidence: 99%

“…Indeed, 8 studies described prospective virtual screening protocols combining several in silico methods for the prediction of dual PPARα/γ agonist ligands with therapeutic applications for T2D ( 70 – 72 ) and of PPARγ ligands ( 74 – 78 ). However, experimental validation was achieved for only 3 of these studies ( 75 – 77 ), which limits the evaluation of the protocols performance. The protocol presented by Kaserer et al.…”

Section: Studied Nuclear Receptorsmentioning

confidence: 99%

“…The implication of this receptor in several pathologies explains the fact that all project specific to PPAR fall under the therapeutic application. Indeed, 8 studies described prospective virtual screening protocols combining several in silico methods for the prediction of dual PPARa/g agonist ligands with therapeutic applications for T2D (70)(71)(72) and of PPARg ligands (74)(75)(76)(77)(78). However, experimental validation was achieved for only 3 of these studies (75)(76)(77), which limits the evaluation of the protocols performance.…”

Section: Peroxisome Proliferator-activated Receptorsmentioning

confidence: 99%

“…Indeed, 8 studies described prospective virtual screening protocols combining several in silico methods for the prediction of dual PPARa/g agonist ligands with therapeutic applications for T2D (70)(71)(72) and of PPARg ligands (74)(75)(76)(77)(78). However, experimental validation was achieved for only 3 of these studies (75)(76)(77), which limits the evaluation of the protocols performance. The protocol presented by Kaserer et al for PPARg partial agonist ligands prediction (76) is of particular interest since a retrospective study was first achieved to select optimal models for the prospective screening.…”

Section: Peroxisome Proliferator-activated Receptorsmentioning

confidence: 99%

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Review of in silico studies dedicated to the nuclear receptor family: Therapeutic prospects and toxicological concerns

et al. 2022

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Being in the center of both therapeutic and toxicological concerns, NRs are widely studied for drug discovery application but also to unravel the potential toxicity of environmental compounds such as pesticides, cosmetics or additives. High throughput screening campaigns (HTS) are largely used to detect compounds able to interact with this protein family for both therapeutic and toxicological purposes. These methods lead to a large amount of data requiring the use of computational approaches for a robust and correct analysis and interpretation. The output data can be used to build predictive models to forecast the behavior of new chemicals based on their in vitro activities. This atrticle is a review of the studies published in the last decade and dedicated to NR ligands in silico prediction for both therapeutic and toxicological purposes. Over 100 articles concerning 14 NR subfamilies were carefully read and analyzed in order to retrieve the most commonly used computational methods to develop predictive models, to retrieve the databases deployed in the model building process and to pinpoint some of the limitations they faced.

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Section: Studied Nuclear Receptorsmentioning

confidence: 99%

Section: Studied Nuclear Receptorsmentioning

confidence: 99%

Section: Peroxisome Proliferator-activated Receptorsmentioning

confidence: 99%

Section: Peroxisome Proliferator-activated Receptorsmentioning

confidence: 99%

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Review of in silico studies dedicated to the nuclear receptor family: Therapeutic prospects and toxicological concerns

et al. 2022

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Structure-Based Stepwise Screening of PPARγ Antagonists as Potential Competitors with NCOA1 Coactivator Peptide for PPARγ CIS Site

Shen

Chi

Zhou

et al. 2018

Int J Pept Res Ther

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Systematic analysis and integrative discovery of active-site subpocket-specific dehydroquinate synthase inhibitors combating antibiotic-resistant Staphylococcus aureus infection

Liu

2018

J. Bioinform. Comput. Biol.

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Shikimate pathway plays an essential role in the biosynthesis of aromatic amino acids in various plants and bacteria, which consists of seven key enzymes and they are all attractive targets for antibacterial agent development due to their absence in humans. The Staphylococcus aureus dehydroquinate synthase (SaDHQS) is involved in the second step of shikimate pathway, which catalyzes the NAD[Formula: see text]-dependent conversion of 3-deoxy-D-arabino-heptulosonate-7-phosphate to dehydroquinate via multiple steps. The enzyme active site can be characterized by two spatially separated subpockets 1 and 2, which represent the reaction center of substrate adduct with NAD[Formula: see text] nicotinamide moiety and the assistant binding site of NAD[Formula: see text] adenine moiety, respectively. In silico virtual screening is performed against a biogenic compound library to discover SaDHQS subpocket-specific inhibitors, which were then tested against both antibiotic-sensitive and antibiotic-resistant S. aureus strains by using in vitro susceptibility test. The activity profile of hit compounds has no considerable difference between the antibiotic-sensitive and -resistant strains. The subpocket 1-specific inhibitors exhibit a generally higher activity than subpocket 2-specific inhibitors, and they also hold a strong selectivity between their cognate and noncognate subpockets. Dynamics and energetics analyses reveal that the SaDHQS active site prefers to interact with amphipathic and polar inhibitors by forming multiple hydrogen bonds and van der Waals packing at the complex interfaces of the two subpockets with their cognate inhibitors.

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Integrated in silico–in vitro screening of ovarian cancer peroxisome proliferator-activated receptor-γ agonists against a biogenic compound library

Cited by 3 publications

References 34 publications

Review of in silico studies dedicated to the nuclear receptor family: Therapeutic prospects and toxicological concerns

Review of in silico studies dedicated to the nuclear receptor family: Therapeutic prospects and toxicological concerns

Structure-Based Stepwise Screening of PPARγ Antagonists as Potential Competitors with NCOA1 Coactivator Peptide for PPARγ CIS Site

Systematic analysis and integrative discovery of active-site subpocket-specific dehydroquinate synthase inhibitors combating antibiotic-resistant Staphylococcus aureus infection

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