molecules-logo

Journal Browser

Journal Browser

Small-Molecule Modulators Targeting Emerging Therapeutic Pathways: Design, Synthesis and Biological Evaluation

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 1573

Special Issue Editor


E-Mail Website
Guest Editor
State Key Laboratory of Drug Research and Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Interests: protein–protein interaction; small-molecule inhibitors; kinase inhibitors; molecular glues; immunomodulators; anticancer therapeutics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the post-genomic era, the therapeutic modalities of human diseases have evolved dramatically. Small-molecule modulators used to be the standard option for defined therapeutic pathways; however, antibodies, nucleotide-based drugs, and cell-based therapies are attracting increasing amounts of attention. Many novel therapeutic targets are emerging driven by advancements in biologic and clinical research, providing new opportunities for small-molecule modulators. For example, the inhibition of cellular protein–protein interactions was once considered undruggable but has now been proven to be workable in light of Venetoclax. In addition, specific cellular protein(s) can now be selectively degraded in the presence of rationally designed PROTACs and/or molecular glues, while small-molecule modulators of human immunity also show great therapeutic promises in human clinical trials. Notwithstanding, small-molecule modulators of enzymes are still a fruitful area of research delivering numerous marketed drugs. One notable example is that more than 70 small-molecule inhibitors of kinases have been approved by the FDA and hundreds of clinical trials are ongoing, testing more novel ones. In view of the dynamic evolution of small-molecule modulators targeting emerging therapeutic pathways, this Special Issue welcomes original research concerning their design, synthesis and biological evaluation

Prof. Dr. Yujun Zhao
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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

  • immunomodulator
  • enzymatic modulator
  • PROTAC
  • molecular glue
  • modulator of PPI
  • receptor agonist
  • receptor antagonist
  • small molecules

Published Papers (2 papers)

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

Research

Jump to: Review

18 pages, 1864 KiB  
Article
Sterol Derivatives Specifically Increase Anti-Inflammatory Oxylipin Formation in M2-like Macrophages by LXR-Mediated Induction of 15-LOX
by Reiichi Ohno, Malwina Mainka, Rebecca Kirchhoff, Nicole M. Hartung and Nils Helge Schebb
Molecules 2024, 29(8), 1745; https://doi.org/10.3390/molecules29081745 - 12 Apr 2024
Viewed by 598
Abstract
The understanding of the role of LXR in the regulation of macrophages during inflammation is emerging. Here, we show that LXR agonist T09 specifically increases 15-LOX abundance in primary human M2 macrophages. In time- and dose-dependent incubations with T09, an increase of 3-fold [...] Read more.
The understanding of the role of LXR in the regulation of macrophages during inflammation is emerging. Here, we show that LXR agonist T09 specifically increases 15-LOX abundance in primary human M2 macrophages. In time- and dose-dependent incubations with T09, an increase of 3-fold for ALOX15 and up to 15-fold for 15-LOX-derived oxylipins was observed. In addition, LXR activation has no or moderate effects on the abundance of macrophage marker proteins such as TLR2, TLR4, PPARγ, and IL-1RII, as well as surface markers (CD14, CD86, and CD163). Stimulation of M2-like macrophages with FXR and RXR agonists leads to moderate ALOX15 induction, probably due to side activity on LXR. Finally, desmosterol, 24(S),25-Ep cholesterol and 22(R)-OH cholesterol were identified as potent endogenous LXR ligands leading to an ALOX15 induction. LXR-mediated ALOX15 regulation is a new link between the two lipid mediator classes sterols, and oxylipins, possibly being an important tool in inflammatory regulation through anti-inflammatory oxylipins. Full article
Show Figures

Graphical abstract

Review

Jump to: Research

11 pages, 247 KiB  
Review
Targeting Moonlighting Enzymes in Cancer
by Chunxu Lin, Mingyang Yu, Ximei Wu, Hui Wang, Min Wei and Luyong Zhang
Molecules 2024, 29(7), 1573; https://doi.org/10.3390/molecules29071573 - 1 Apr 2024
Viewed by 744
Abstract
Moonlighting enzymes are multifunctional proteins that perform multiple functions beyond their primary role as catalytic enzymes. Extensive research and clinical practice have demonstrated their pivotal roles in the development and progression of cancer, making them promising targets for drug development. This article delves [...] Read more.
Moonlighting enzymes are multifunctional proteins that perform multiple functions beyond their primary role as catalytic enzymes. Extensive research and clinical practice have demonstrated their pivotal roles in the development and progression of cancer, making them promising targets for drug development. This article delves into multiple notable moonlighting enzymes, including GSK-3, GAPDH, and ENO1, and with a particular emphasis on an enigmatic phosphatase, PTP4A3. We scrutinize their distinct roles in cancer and the mechanisms that dictate their ability to switch roles. Lastly, we discuss the potential of an innovative approach to develop drugs targeting these moonlighting enzymes: target protein degradation. This strategy holds promise for effectively tackling moonlighting enzymes in the context of cancer therapy. Full article
Show Figures

Graphical abstract

Back to TopTop