New Frontiers in Marine-Derived Kinase Modulators

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (31 May 2019) | Viewed by 6763

Special Issue Editor


E-Mail Website
Guest Editor
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA
Interests: olive phenolics; optimization of bioactive natural product scaffolds; breast cancer migration, invasion, metastasis and recurrence; c-Met/HGF pathway; PCSK9-LDLR interaction inhibitors; computer-aided/rational semisynthetic optimizations of natural products
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Protein kinases are high-affinity cell receptors for several key polypeptide growth factors, cytokines, and hormones. Protein kinases usually have a common kinase catalytic domain, which plays a major role in their cellular functions, including cell shape, survival, and others. Protein kinases may also be associated with additional non-kinase domains, which confer additional selectivity, biological activity, subcellular localization, and binding with other proteins. There are several hundred genes encoding members of the kinase family in the human genome.

Several kinases share similar molecular architectures. Growth factors binding to the kinases induce possible dimerization, activation of their kinase domains through auto-phosphorylation, and generation of binding sites for a series of cytosolic proteins, containing polypeptide segments recruited to activated receptors. These proteins subsequently generate a cascade of events leading to various critical normal and/or pathological cellular responses, such as cell proliferation, migration, differentiation, survival, neovascularization, and tissue repair. Therefore, dysregulated or constitutively activated protein kinases are excellent molecular targets for different targeted therapies in numerous oncological, neurological, and other important human diseases.  

About 50% of today’s pharmaceuticals are natural products or analogs modeled based on or inspired by a natural product parent. Marine natural products have unmatched chemical and biological diversities, unique pharmacophoric features, and chemical space. This Special Issue, entitled “New Frontiers in Marine-Derived Kinase Modulators”, is calling for scientific innovations utilizing marine natural products to modulate protein kinases for different therapeutic directions. Marine Drugs hopes that this Special Issue will attract the attention of the scientific community for the important and unique role of marine natural products as potential future drug entity candidates through selective and differential modulation of diverse protein kinases by marine natural products.

Prof. Dr. Khalid A. El Sayed
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • binding
  • biochemical effects
  • cellular
  • dysregulations
  • enhancers
  • inhibitors
  • kinases
  • marine natural products
  • modulator
  • mutation
  • neurological
  • pharmacophore

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (1 paper)

Order results
Result details
Select all
Export citation of selected articles as:

Research

23 pages, 4826 KiB  
Article
Predicting Blood–Brain Barrier Permeability of Marine-Derived Kinase Inhibitors Using Ensemble Classifiers Reveals Potential Hits for Neurodegenerative Disorders
by Fabien Plisson and Andrew M. Piggott
Mar. Drugs 2019, 17(2), 81; https://doi.org/10.3390/md17020081 - 29 Jan 2019
Cited by 36 | Viewed by 6247
Abstract
The recent success of small-molecule kinase inhibitors as anticancer drugs has generated significant interest in their application to other clinical areas, such as disorders of the central nervous system (CNS). However, most kinase inhibitor drug candidates investigated to date have been ineffective at [...] Read more.
The recent success of small-molecule kinase inhibitors as anticancer drugs has generated significant interest in their application to other clinical areas, such as disorders of the central nervous system (CNS). However, most kinase inhibitor drug candidates investigated to date have been ineffective at treating CNS disorders, mainly due to poor blood–brain barrier (BBB) permeability. It is, therefore, imperative to evaluate new chemical entities for both kinase inhibition and BBB permeability. Over the last 35 years, marine biodiscovery has yielded 471 natural products reported as kinase inhibitors, yet very few have been evaluated for BBB permeability. In this study, we revisited these marine natural products and predicted their ability to cross the BBB by applying freely available open-source chemoinformatics and machine learning algorithms to a training set of 332 previously reported CNS-penetrant small molecules. We evaluated several regression and classification models, and found that our optimised classifiers (random forest, gradient boosting, and logistic regression) outperformed other models, with overall cross-validated model accuracies of 80%–82% and 78%–80% on external testing. All 3 binary classifiers predicted 13 marine-derived kinase inhibitors with appropriate physicochemical characteristics for BBB permeability. Full article
(This article belongs to the Special Issue New Frontiers in Marine-Derived Kinase Modulators)
Show Figures

Graphical abstract

Back to TopTop