Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
4.9
Journals
IJMS
Special Issues
25th Anniversary of IJMS: Updates and Advances in Molecular...
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

25th Anniversary of IJMS: Updates and Advances in Molecular Pharmacology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 7600

Special Issue Editor

Prof. Dr. Roberto Scatena

E-Mail Website
Guest Editor
Dipartimento di Medicina di Laboratorio, Madre Giuseppina Vannini Hospital, Via di Acqua Bullicante 4, 00177 Rome, Italy
Interests: cancer; biomarkers; mitochondria; targeted drugs; clinical chemistry; laboratory medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The field of molecular pharmacology is rapidly transforming, driven by innovative technologies that reshape our understanding of drug-target interactions and push towards novel therapeutic approaches. We are entering a new era of pharmacology, moving beyond traditional small-molecule inhibitors/activators. New techniques (i.e., cryo-electron microscopy -Cryo-EM-) permit atomic-level visualization of drug binding to biological components as proteins, ameliorating drug design. Moreover, the introduction of 'omics' technologies—genomics, proteomics, and transcriptomics—is advancing pharmacogenomics, allowing precise predictions of drug responses and toxicities for individuals (i.e., personelized pharmacology).

Most importantly, the therapeutic landscape is evolving with new drug modalities derived from genetic approaches. RNA-based therapeutics, including siRNA, ASO, and mRNA, allow for direct modulation of gene expression in previously “undruggable” pathways. Breakthroughs in targeted protein degradation through PROTACs and “molecular glues” enable the elimination of toxic proteins. At last but not least, the integration of these biological advances with artificial intelligence  will accelerate the drug discovery pipeline. These advancements represent a fundamental steps towards a more specific, personalized, and effective treatments for various human diseases.

Prof. Dr. Roberto Scatena
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 250 words) can be sent to the Editorial Office for assessment.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • precision medicine
  • pharmacogenomics
  • targeted protein degradation (TPD)
  • molecular pharmacology
  • RNA Therapeutics
  • novel drug modalities
  • proteomics
  • transcriptomics
  • personalized drug therapy

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.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

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

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

20 pages, 3827 KB  
Article
New N-Heterocyclic Carbene Gold and Platinum Complexes with 1,3-Dialkyl-4-anisyl-5-(4-chlorophenyl)imidazol-2-ylidene Ligands for the Treatment of Esophageal Adenocarcinoma
by Hindole Ghosh, Tobias Rehm, Sangita Bhattacharyya, Miru Lee, Dileepkumar Veeragoni, Rainer Schobert, Bernhard Biersack and Prasad Dandawate
Int. J. Mol. Sci. 2026, 27(4), 2032; https://doi.org/10.3390/ijms27042032 - 21 Feb 2026
Viewed by 437
Abstract
Encouraged by the promising anticancer activity of a iodidogold(I)-N-heterocyclic carbene (NHC) complex with a 1,3-diethyl-4-anisyl-5-(4-chlorophenyl)imidazol-2-ylidene ligand system, a series of new gold(I), gold(III) and platinum(II) complexes coordinated to this ligand system were designed, prepared, and characterized using NMR spectroscopy and mass [...] Read more.
Encouraged by the promising anticancer activity of a iodidogold(I)-N-heterocyclic carbene (NHC) complex with a 1,3-diethyl-4-anisyl-5-(4-chlorophenyl)imidazol-2-ylidene ligand system, a series of new gold(I), gold(III) and platinum(II) complexes coordinated to this ligand system were designed, prepared, and characterized using NMR spectroscopy and mass spectrometry methods. A preliminary anticancer screening of the complexes using four esophageal adenocarcinoma (EAC) cell lines showed promising activities for the cationic triphenylphosphino-NHC-gold(I) and bis-NHC-gold(I) complexes, accompanied by strong antiproliferative, colony-, and spheroid-forming inhibitory effects. The compounds were relatively less toxic to the normal esophageal cell line Het-1A and the monocyte cell line THP-1. Moreover, these compounds induced caspase 3/7 activity and downregulated anti-apoptotic proteins (Bcl-XL, Bcl-2, and Mcl-1) in EAC cells. Further, the cell cycle promoter cyclin D1 was suppressed by these NHC-gold(I) complexes. Finally, we observed strong reactive oxygen species (ROS) induction in EAC cells with NHC-gold(I) complexes 8 and 11. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pharmacology)
►▼ Show Figures

Figure 1

10 pages, 1670 KB  
Article
Fyn–Saracatinib Complex Structure Reveals an Active State-like Conformation
by Hai Minh Ta, Banumathi Sankaran, Eric D. Roush, Josephine C. Ferreon, Allan Chris M. Ferreon and Choel Kim
Int. J. Mol. Sci. 2026, 27(3), 1143; https://doi.org/10.3390/ijms27031143 - 23 Jan 2026
Viewed by 559
Abstract
Fyn is a Src-family tyrosine kinase implicated in synaptic dysfunction and neuroinflammation across multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Saracatinib (AZD0530) is a potent Src-family inhibitor that has been explored as a repurposed therapeutic; however, its clinical utility [...] Read more.
Fyn is a Src-family tyrosine kinase implicated in synaptic dysfunction and neuroinflammation across multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Saracatinib (AZD0530) is a potent Src-family inhibitor that has been explored as a repurposed therapeutic; however, its clinical utility is limited by poor kinase selectivity caused by high sequence conservation within Src-family ATP-binding sites. Here, we combine surface plasmon resonance (SPR) and X-ray crystallography to define saracatinib recognition by the Fyn kinase domain (KD). SPR single-cycle kinetics shows that saracatinib binds the isolated Fyn KD and full-length Fyn with low-nanomolar affinity, whereas dasatinib binds with subnanomolar affinity and markedly slower dissociation. We determined the crystal structure of the Fyn KD-saracatinib complex at 2.22 Å resolution. The kinase adopts an active-like conformation with the DFG motif and αC-helix in the ‘in’ state and a conserved β3 αC Lys-Glu salt bridge. Saracatinib occupies the adenine and ribose pockets, and engages the hinge through direct and water-mediated hydrogen bonding while complementing a hydrophobic back pocket by van der Waals contacts. Comparison with reported saracatinib-bound structures of other kinases suggests that the active-state geometry observed for Fyn creates a pocket not observed in inactive-like complexes, providing a structural handle for designing Fyn-selective inhibitors. Comparison with all saracatinib-bound kinase co-structures currently available in the PDB (ALK2 and PKMYT1) indicates a conserved monodentate hinge binding mode but kinase-dependent αC-helix conformations, providing a structural rationale for designing Fyn-selective analogues. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pharmacology)
►▼ Show Figures

Figure 1

18 pages, 1926 KB  
Article
Evaluation of 2,7-Naphthyridines as Targeted Anti-Staphylococcal Candidates with Microbiota-Sparing Properties
by Anna Wójcicka, Maciej Spiegel, Bartłomiej Dudek, Malwina Brożyna, Adam Junka and Marcin Mączyński
Int. J. Mol. Sci. 2025, 26(21), 10442; https://doi.org/10.3390/ijms262110442 - 27 Oct 2025
Viewed by 852
Abstract
The rising resistance of bacterial and fungal strains, particularly in biofilm form, is diminishing the efficacy of available therapies and poses a major threat to human health. This highlights the need for new antimicrobial agents. A review of biological studies has shown that [...] Read more.
The rising resistance of bacterial and fungal strains, particularly in biofilm form, is diminishing the efficacy of available therapies and poses a major threat to human health. This highlights the need for new antimicrobial agents. A review of biological studies has shown that 2,7-naphthyridine derivatives exhibit a wide spectrum of pharmacological properties, including antimicrobial activity, which has contributed to the development of new compounds containing this scaffold. In this work, the obtained compounds were tested to assess their ability to eradicate biofilm formed by selected reference strains of opportunistic pathogens: Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans as well as towards normal microbiota representative, referred to as the Lactobacillus crispatus. The tested 2,7-naphthyridine derivatives showed selective antimicrobial activity, exclusively against S. aureus. 10j demonstrated the highest, among tested compounds, activity on this pathogen (MIC = 8 mg/L), while compound 10f exhibited ~100-fold stronger activity (MIC = 31 mg/L) than the majority of the library compounds. The in vitro assessment on fibroblast cell lines demonstrated low cytotoxicity of both compounds 10f and 10j, which was subsequently confirmed in vivo using the Galleria mellonella larval model, where no signs of systemic toxicity were observed during the 5-day observation period. Due to the structural similarity of the compounds 10f and 10j to typical gyrase/topoisomerase IV inhibitors, molecular dynamics simulations were performed on a ternary complex containing protein, DNAds, and a 1,5-naphthyridine inhibitor (PDB ID: 6Z1A). Molecular dynamics of the gyrase–DNA ternary complex supported stable binding of both hydrazone derivatives, with 10j showing slightly more favorable MM/GBSA energetics driven by electrostatics and halogen bonding, consistent with its ~4-fold lower MIC versus 10f. Taken together, our data highlight compound 10j as a promising microbiota-sparing antibacterial candidate, particularly suitable for selective interventions against S. aureus, for instance in vaginal infections, where targeted eradication of the pathogen without disturbing protective commensals is highly desirable. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pharmacology)
►▼ Show Figures

Figure 1

Review

Jump to: Research

22 pages, 790 KB  
Review
A Comprehensive Review of Natural Products Against Allergic Rhinitis and Asthma: From Sensitization to Chronic Remodeling
by Xuesong Zhang, Wenchu Zhou, Jie Zhang and Chenggang Liu
Int. J. Mol. Sci. 2026, 27(7), 3171; https://doi.org/10.3390/ijms27073171 - 31 Mar 2026
Viewed by 570
Abstract
Allergic rhinitis (AR) and allergic asthma are chronic airway inflammatory diseases characterized by three phases: sensitization, acute exacerbation, and chronic remodeling. While conventional antiallergic drugs provide symptomatic relief, they often face limitations including drug resistance, side effects, and inability to reverse chronic airway [...] Read more.
Allergic rhinitis (AR) and allergic asthma are chronic airway inflammatory diseases characterized by three phases: sensitization, acute exacerbation, and chronic remodeling. While conventional antiallergic drugs provide symptomatic relief, they often face limitations including drug resistance, side effects, and inability to reverse chronic airway remodeling. Natural products have emerged as promising therapeutic alternatives due to their multi-target effects and safety profiles. This review systematically summarizes natural small molecules targeting distinct pathological mechanisms across the three phases of AR and asthma, introducing a chronopharmacological perspective for stage-specific therapeutic strategies. During sensitization, flavonoids (quercetin, luteolin, apigenin, baicalin) and polyphenols (curcumin, resveratrol) target the epithelial–dendritic cell axis by suppressing alarmin release and blocking dendritic cell maturation. In acute exacerbation, flavonoids (hispidulin, quercetin) and isoquinoline alkaloids (coptisine) exhibit rapid intervention through mast cell stabilization and neurogenic inflammation suppression. In chronic remodeling, stilbenes (resveratrol) and flavones (baicalin, baicalein) reverse established structural changes through TGF-β1/Smad, PTEN/PI3K/AKT, and PDGF-BB/PDGFR-β pathways. Mapping natural compounds to specific disease stages provides a molecular basis for precision medicine approaches. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pharmacology)
►▼ Show Figures

Figure 1

25 pages, 873 KB  
Review
Potential Links Between Aging, Mitochondrial Dysfunction, and Drug Transporter Function—Molecular Mechanisms and Pharmacokinetic Implications
by Patryk Rzeczycki, Oliwia Pęciak, Martyna Plust and Marek Droździk
Int. J. Mol. Sci. 2026, 27(5), 2206; https://doi.org/10.3390/ijms27052206 - 26 Feb 2026
Viewed by 565
Abstract
Aging is associated with complex physiological changes that influence drug pharmacokinetics, including alterations in mitochondrial function and gastrointestinal (GI) drug transporter activity. Mitochondrial dysfunction—characterized by reduced oxidative phosphorylation, mitochondrial DNA damage, and increased reactive oxygen species—is a hallmark of aging and may affect [...] Read more.
Aging is associated with complex physiological changes that influence drug pharmacokinetics, including alterations in mitochondrial function and gastrointestinal (GI) drug transporter activity. Mitochondrial dysfunction—characterized by reduced oxidative phosphorylation, mitochondrial DNA damage, and increased reactive oxygen species—is a hallmark of aging and may affect energy- and redox-dependent cellular processes in the gut. At the same time, aging can modulate the expression and function of key intestinal drug transporters from the ATP-binding cassette (ABC) and solute carrier (SLC) families, which play a central role in oral drug absorption and bioavailability. This review examines the molecular links between age-related mitochondrial dysfunction and regulation of GI drug transporters, with a focus on their pharmacokinetic consequences in older adults. We summarize evidence of mitochondrial decline in the aging intestine and discuss how mitochondrial signals—such as cellular energy status and oxidative stress—regulate transporter expression and activity via pathways including AMPK (AMP-Activated Protein Kinase), Sirtuin–FOXO (Forkhead box O transcription factors), Nrf2 (Nuclear factor erythroid 2-related factor 2), and NF-κB (Nuclear Factor kappa B). We highlight clinical examples of drugs showing age-related changes in bioavailability that may be attributable to transporter dysfunction. Finally, we discuss therapeutic implications for geriatric pharmacotherapy, including dose adjustment, management of transporter-mediated drug–drug interactions, and strategies aimed at preserving mitochondrial health. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pharmacology)
►▼ Show Figures

Figure 1

22 pages, 1864 KB  
Review
Chimeric Approach to Identify Molecular Determinants of Nicotinic Acetylcholine Receptors
by Pooja Sapkota, Seyedeh Melika Akaberi, Biwash Ghimire and Kavita Sharma
Int. J. Mol. Sci. 2026, 27(2), 1091; https://doi.org/10.3390/ijms27021091 - 22 Jan 2026
Viewed by 672
Abstract
Nicotinic acetylcholine receptors (nAChRs) are membrane-bound proteins that mediate fast synaptic transmission throughout the nervous system. A functional nAChR subtype is formed by the combination of multiple subunits arranged as homomeric or heteromeric pentamers, each with a distinct pharmacological profile. Disruption of their [...] Read more.
Nicotinic acetylcholine receptors (nAChRs) are membrane-bound proteins that mediate fast synaptic transmission throughout the nervous system. A functional nAChR subtype is formed by the combination of multiple subunits arranged as homomeric or heteromeric pentamers, each with a distinct pharmacological profile. Disruption of their neurotransmission contributes to various neuropathologies, emphasizing the need for detailed knowledge of receptor structure, function, subunit composition, dynamics, and potential ligand-binding sites. However, their structural complexity as integral membrane proteins has hindered expression in mammalian cell lines and proven even more challenging to crystallize, limiting insights into ligand interactions. Understanding the molecular determinants governing nAChRs function is essential for the rational design of selective therapeutics targeting neurological disorders. The emergence of a chimeric receptor approach has dramatically improved the ability to study these important proteins and opened new avenues for high-throughput screening in drug discovery efforts. This review explains how the design of chimera constructs using soluble homologs, such as AChBP, provides researchers with an immense opportunity to investigate receptor structure–function relationships and subtype-specific properties, thereby facilitating the development of more effective treatments. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pharmacology)
►▼ Show Figures

Graphical abstract

20 pages, 1344 KB  
Review
Deep Generative AI for Multi-Target Therapeutic Design: Toward Self-Improving Drug Discovery Framework
by Soo Im Kang, Jae Hong Shin, Benjamin M. Wu and Hak Soo Choi
Int. J. Mol. Sci. 2025, 26(23), 11443; https://doi.org/10.3390/ijms262311443 - 26 Nov 2025
Cited by 6 | Viewed by 2825
Abstract
Multi-target drug design represents a paradigm shift in tackling the complexity and heterogeneity of diseases such as cancer. Conventional single-target therapies frequently face limitations due to network redundancy, pathway compensation, and adaptive resistance mechanisms. In contrast, deep generative models, empowered by advanced artificial [...] Read more.
Multi-target drug design represents a paradigm shift in tackling the complexity and heterogeneity of diseases such as cancer. Conventional single-target therapies frequently face limitations due to network redundancy, pathway compensation, and adaptive resistance mechanisms. In contrast, deep generative models, empowered by advanced artificial intelligence algorithms, provide scalable and versatile platforms for the de novo generation and optimization of small molecules with activity across multiple therapeutic targets. This review provides a comprehensive overview of the recent landscape of AI-driven deep generative modeling for multi-target drug discovery, highlighting breakthroughs in model architectures, molecular representations, and goal-directed optimization strategies. We also examine the emergence of self-improving learning systems, closed-loop frameworks that iteratively refine molecular candidates through integrated feedback, as a transformative approach to adaptive drug design. Finally, key challenges, current limitations, and emerging trends are discussed to guide the evolution of next-generation intelligent and autonomous drug discovery pipelines for multi-target therapeutics. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pharmacology)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop