Research in Pharmacological Therapies, 2nd Edition

Topic Information

Dear Colleagues,

Drugs are bioactive compounds that are present in chemical structures in both the plant and animal kingdoms. Both organic and inorganic compounds have been used empirically to cure diseases or to treat the symptoms that are derived from them. Much of modern pharmacology has its origins in these types of compounds. Due to advancements in chemistry, we are able to characterize the chemical composition of any compound with a high degree of accuracy. In fact, to this day, we are continuing to discover new compounds in nature that demonstrate very promising pharmacological activities, which could lay the foundation for new, more efficient, and more effective bioactive molecules through chemical modifications. Furthermore, pharmacology is advancing as new synthetic compounds with increasingly specific and effective pharmacological properties are being developed at a rapid pace. Therefore, as a part of this topic, we plan to collect the latest advances in new drugs of either natural or synthetic origin in addition to describing their biological targets, their specific mechanisms of action, and their effective dosages.

Dr. Juan Gambini
Dr. Ángel Luis Ortega
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	3.9	6.8	2013	21 Days	CHF 2600	Submit
International Journal of Molecular Sciences ijms	4.9	9.0	2000	17.8 Days	CHF 2900	Submit
Medicines medicines	-	-	2014	27.7 Days	CHF 1400	Submit
Pharmaceuticals pharmaceuticals	4.8	7.7	2004	16 Days	CHF 2900	Submit
Scientia Pharmaceutica scipharm	2.5	4.6	1930	22.8 Days	CHF 1000	Submit

Preprints.org is a multidisciplinary platform offering a preprint service designed to facilitate the early sharing of your research. It supports and empowers your research journey from the very beginning.

MDPI Topics is collaborating with Preprints.org and has established a direct connection between MDPI journals and the platform. Authors are encouraged to take advantage of this opportunity by posting their preprints at Preprints.org prior to publication:

1. Share your research immediately: disseminate your ideas prior to publication and establish priority for your work.
2. Safeguard your intellectual contribution: Protect your ideas with a time-stamped preprint that serves as proof of your research timeline.
3. Boost visibility and impact: Increase the reach and influence of your research by making it accessible to a global audience.
4. Gain early feedback: Receive valuable input and insights from peers before submitting to a journal.
5. Ensure broad indexing: Web of Science (Preprint Citation Index), Google Scholar, Crossref, SHARE, PrePubMed, Scilit and Europe PMC.

Related Topic

Published Papers (7 papers)

Order results

Content type Publication Date

Result details

Normal Extended Compact

Journals

All Biomedicines IJMS Medicines Pharmaceuticals Sci. Pharm.

Show export options expand_more Show export options expand_less

Select all

Export citation of selected articles as:

Plain Text BibTeX BibTeX (without abstracts) Endnote Endnote (without abstracts) Tab-delimited RIS

Error

Oops... you haven't selected anything for export.

Ok

clear

attachment

Supplementary material:
Supplementary File 1 (ZIP, 674 KB)

16 pages, 3048 KB  

Open AccessArticle

Quantification of In Vitro Replicative Lifespan Elongation Activity of Hormones, Antioxidants, Plant Extract and Bacterial Exudate by Updated “Overlay Method”

by Hiroshi Sakagami, Masayo Abe, Megumi Inomata, Hideki Aoyagi, Takao Tsukahara, Kenjiro Bandow, Shogo Nishino, Hiroshi Kadokura, Yuka Kato and Satoshi Yokose

Medicines 2026, 13(2), 12; https://doi.org/10.3390/medicines13020012 - 30 Mar 2026

Viewed by 269

Abstract

Background/Objectives: Many products that claim to have anti-aging effects have been reported, but their relative potency is not clear. In this study, the in vitro replicative lifespan extension (RLE) activity of various groups of physiologically active substances was compared by using the [...] Read more.

Background/Objectives: Many products that claim to have anti-aging effects have been reported, but their relative potency is not clear. In this study, the in vitro replicative lifespan extension (RLE) activity of various groups of physiologically active substances was compared by using the updated “overlay method”. Methods: Human dermal and periodontal ligament fibroblasts (HDFa, HPLF) were inoculated into the inner 60 wells of 96-well microplate, surround by sterile water to prevent the water evaporation. At Day 1 and Day 8, the cells were overlayed with wide ranges of concentrations (0.01–100 µM) of samples without medium change. Viable cell number was measured by the MTT method at Day 15 and then corrected for the variation in cell growth due to the location of inoculated cells. The RLE value was calculated as the maximum cell proliferation rate relative to the control. Results: Cell density of HDFa and HPLFs at subculture decreased with the passage number, and their growth was stopped at 56 or 85 population doubling levels (PDLs), respectively. Hydrocortisone showed the highest RLE values among six hormones, followed by three plant extracts, sodium ascorbate and quercetin. On the other hand, other antioxidants, chlorogenic acid, phenylpropanoids, vanilloids, and bacterial products showed little or no RLE effects. However, for HPLF cells, hydrocortisone did not show RLE effects while oxytocin showed slight stimulation. Conclusions: When differences in proliferation due to cell seeding position were corrected, the biphasic dose response curve of most of the compounds significantly reduced. The present study suggests the significant role of hormones for the regulation of the long-term aging process. To confirm systemic or clinical anti-aging effects, further in vitro and in vivo experiments are needed. Full article

(This article belongs to the Topic Research in Pharmacological Therapies, 2nd Edition)

►▼ Show Figures

Figure 1

28 pages, 2382 KB  

Open AccessReview

Once-Monthly and Extended-Interval Incretin-, Amylin-, and THRβ-Targeting Therapies for Type 2 Diabetes and Obesity: Clinical Evidence and Development Pipelines

by Héctor Iván Saldívar-Cerón

Sci. Pharm. 2026, 94(1), 21; https://doi.org/10.3390/scipharm94010021 - 4 Mar 2026

Viewed by 1680

Abstract

Once-monthly injectable therapies targeting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and adjacent metabolic pathways are moving from a conceptual goal to a plausible next step for type 2 diabetes (T2D) and obesity. The most clinically advanced program is maridebart cafraglutide (MariTide), a [...] Read more.

Once-monthly injectable therapies targeting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and adjacent metabolic pathways are moving from a conceptual goal to a plausible next step for type 2 diabetes (T2D) and obesity. The most clinically advanced program is maridebart cafraglutide (MariTide), a long-acting GLP-1 receptor agonist conjugated to an Fc-containing scaffold that also mediates sustained GIP receptor antagonism. Across phase 2 trials, once-monthly maridebart has produced clinically meaningful weight loss (~12–16% in adults without diabetes; ~8–12% in those with T2D), together with HbA1c reductions of ~1.2–1.6 percentage points, with a safety profile broadly consistent with GLP-1-based therapy. An exploratory every-8-weeks regimen showed attenuated efficacy, suggesting that monthly dosing may represent a practical lower boundary for maintaining therapeutic exposure and metabolic effect in this format. Beyond maridebart, a rapidly expanding pipeline—including ultra-long-acting GLP-1 analogs, dual GLP-1/GIP agonists, long-acting GIPR antagonists, amylin receptor agonists, and emerging thyroid hormone receptor beta (THRβ) agonists—is actively testing monthly regimens or induction-to-monthly maintenance strategies; however, most readouts remain early and are frequently limited to conference presentations or sponsor communications. Accordingly, much of the pipeline evidence should be interpreted as early-phase and non-peer-reviewed, and therefore hypothesis-generating. Key uncertainties include long-term durability, cardiometabolic outcomes, immunogenicity, and interindividual variability in response, which will ultimately determine how once-monthly regimens integrate with established weekly standards in routine care. Full article

(This article belongs to the Topic Research in Pharmacological Therapies, 2nd Edition)

►▼ Show Figures

Graphical abstract

attachment

Supplementary material:
Supplementary File 1 (ZIP, 624 KB)

18 pages, 2115 KB  

Open AccessArticle

Hidden Activities of Tyrosine Phenol-Lyase and Tryptophan Indole-Lyase: Recombinant PLP-Dependent C–C Lyases as New Biocatalysts for Antimicrobial Thiosulfinate Generation

by Vitalia V. Kulikova, Svetlana V. Revtovich, Kseniya P. Levshina, Yaroslav V. Kozmenko, Natalya V. Anufrieva, Elena A. Morozova and Pavel N. Solyev

Pharmaceuticals 2026, 19(2), 291; https://doi.org/10.3390/ph19020291 - 10 Feb 2026

Viewed by 521

Abstract

Background: Lyases are used in a wide scope of applications, making them invaluable tools in both industrial biotechnology and molecular biology. Many examples of lyases belong to the extensive family of pyridoxal 5′-phosphate (PLP)-dependent enzymes, which catalyze numerous reactions involved in amino acid [...] Read more.

Background: Lyases are used in a wide scope of applications, making them invaluable tools in both industrial biotechnology and molecular biology. Many examples of lyases belong to the extensive family of pyridoxal 5′-phosphate (PLP)-dependent enzymes, which catalyze numerous reactions involved in amino acid metabolism, like tryptophan indole-lyase (Trpase or Tnase), tyrosine phenol-lyase (TPL), and methionine γ-lyase (MGL). Beyond their role in physiological processes, these lyases can also facilitate the synthesis of other biologically active products from non-canonical substrates. Objectives: Up till now there were only two C–S lyases known for the thiosulfinates’ biosynthesis from S-substituted L-cysteine sulfoxides—alliinase and MGL. Our study reveals for the first time that C–C lyases are capable of C–S lyase activity in reactions with S-alkyl, S-allyl and S-benzyl cysteine sulfoxides. Methods: We have compared the kinetic profiles of S-substituted L-cysteine sulfoxide degradation mediated by carbon–sulfur lyase MGL versus carbon–carbon lyases TPL and Trpase. Results: Among other S-alkyl-L-cysteine sulfoxides, petiveriin (S-benzyl-L-cysteine sulfoxide) was proven to be a substrate for all three enzymes. The potential utility of these enzymes in thiosulfinate production was supported by in vitro testing of enzyme-generated thiosulfinates against clinically relevant pathogens such as Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. Conclusions: Both C–S and C–C lyases—MGL, TPL, and Trpase—can be implemented for practical application in thiosulfinate synthesis. Full article

(This article belongs to the Topic Research in Pharmacological Therapies, 2nd Edition)

►▼ Show Figures

Figure 1

34 pages, 765 KB  

Open AccessReview

Transcription Factors and Methods for the Pharmacological Correction of Their Activity

by Svetlana V. Guryanova, Tatiana V. Maksimova and Madina M. Azova

Int. J. Mol. Sci. 2025, 26(13), 6394; https://doi.org/10.3390/ijms26136394 - 2 Jul 2025

Cited by 10 | Viewed by 4612

Abstract

Transcription factors (TFs) are proteins that control gene expression by binding to specific DNA sequences and are essential for cell development, differentiation, and homeostasis. Dysregulation of TFs is implicated in numerous diseases, including cancer, autoimmune disorders, and neurodegeneration. While TFs were traditionally considered [...] Read more.

Transcription factors (TFs) are proteins that control gene expression by binding to specific DNA sequences and are essential for cell development, differentiation, and homeostasis. Dysregulation of TFs is implicated in numerous diseases, including cancer, autoimmune disorders, and neurodegeneration. While TFs were traditionally considered “undruggable” due to their lack of well-defined binding pockets, recent advances have made it possible to modulate their activity using diverse pharmacological strategies. Major TF families include NF-κB, p53, STATs, HIF-1α, AP-1, Nrf2, and nuclear hormone receptors, which take part in the regulation of inflammation, tumor suppression, cytokine signaling, hypoxia and stress response, oxidative stress, and hormonal response, respectively. TFs can perform multiple functions, participating in the regulation of opposing processes depending on the context. NF-κB, for instance, plays dual roles in immunity and cancer, and is targeted by proteasome and IKKβ inhibitors. p53, often mutated in cancer, is reactivated using MDM2 antagonist Nutlin-3, refunctionalizing compound APR-246, or stapled peptides. HIF-1α, which regulates hypoxic responses and angiogenesis, is inhibited by agents like acriflavine or stabilized in anemia therapies by HIF-PHD inhibitor roxadustat. STATs, especially STAT3 and STAT5, are oncogenic and targeted via JAK inhibitors or novel PROTAC degraders, for instance SD-36. AP-1, implicated in cancer and arthritis, can be inhibited by T-5224 or kinase inhibitors JNK and p38 MAPK. Nrf2, a key antioxidant regulator, can be activated by agents like DMF or inhibited in chemoresistant tumors. Pharmacological strategies include direct inhibitors, activators, PROTACs, molecular glues, and epigenetic modulators. Challenges remain, including the structural inaccessibility of TFs, functional redundancy, off-target effects, and delivery barriers. Despite these challenges, transcription factor modulation is emerging as a viable and promising therapeutic approach, with ongoing research focusing on specificity, safety, and efficient delivery methods to realize its full clinical potential. Full article

(This article belongs to the Topic Research in Pharmacological Therapies, 2nd Edition)

►▼ Show Figures

Figure 1

24 pages, 2661 KB  

Open AccessReview

Oral Small-Molecule GLP-1 Receptor Agonists: Mechanistic Insights and Emerging Therapeutic Strategies

by Héctor Iván Saldívar-Cerón, Jorge Arturo Vargas-Camacho, Sonia León-Cabrera, Paola Briseño-Díaz, Ari Evelyn Castañeda-Ramírez, Axel Eduardo Muciño-Galicia and María Regina Díaz-Domínguez

Sci. Pharm. 2025, 93(2), 26; https://doi.org/10.3390/scipharm93020026 - 11 Jun 2025

Cited by 6 | Viewed by 22589

Abstract

Small-molecule glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent an innovative advancement in oral therapeutics, addressing key limitations associated with injectable peptide-based incretin therapies. These nonpeptidic agents exert their actions primarily through non-canonical binding orthosteric sites within the GLP-1 receptor transmembrane domain, enabling selective G [...] Read more.

Small-molecule glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent an innovative advancement in oral therapeutics, addressing key limitations associated with injectable peptide-based incretin therapies. These nonpeptidic agents exert their actions primarily through non-canonical binding orthosteric sites within the GLP-1 receptor transmembrane domain, enabling selective G protein (Gs)-biased signaling with reduced β-arrestin-mediated adverse effects. Orforglipron has notably advanced through Phase 3 clinical development, demonstrating significant reductions in hemoglobin A1c and body weight (up to 7.9%) with favorable tolerability. Conversely, promising candidates such as danuglipron and lotiglipron were discontinued due to hepatotoxicity, underscoring critical safety concerns intrinsic to small-molecule GLP-1RA development. Current clinical candidates, including GSBR-1290, CT-996, and ECC5004, continue to offer substantial potential due to their oral bioavailability, simplified dosing regimens, and favorable gastrointestinal tolerability. Nevertheless, challenges persist regarding hepatic safety, pharmacodynamic variability, and limited long-term outcome data. This review integrates current structural, pharmacological, and clinical evidence, highlights key mechanistic innovations—including biased agonism, covalent binding strategies, and allosteric modulation—and discusses future directions for this rapidly evolving therapeutic class in metabolic disease management. Full article

(This article belongs to the Topic Research in Pharmacological Therapies, 2nd Edition)

►▼ Show Figures

Graphical abstract

8 pages, 945 KB  

Open AccessCase Report

Triple Non-Statin Therapy with Ezetimibe, Inclisiran, and Bempedoic Acid in Patients with Genetically Confirmed Statin-Induced Rhabdomyolysis: A Dual Case Report

by Jozef Dodulík, Jiří Plášek, Ivana Kacířová, Romana Uřinovská, Jiří Vrtal and Jan Václavík

Pharmaceuticals 2025, 18(6), 818; https://doi.org/10.3390/ph18060818 - 29 May 2025

Cited by 1 | Viewed by 3766

Abstract

Background: Statin intolerance is a serious therapeutic dilemma in secondary cardiovascular prevention (e.g., ESC/EAS Guidelines 2023). This is especially true when confirmed by genetic predisposition and complicated by rhabdomyolysis. Although several non-statin agents have become available in recent years, evidence regarding their combined [...] Read more.

Background: Statin intolerance is a serious therapeutic dilemma in secondary cardiovascular prevention (e.g., ESC/EAS Guidelines 2023). This is especially true when confirmed by genetic predisposition and complicated by rhabdomyolysis. Although several non-statin agents have become available in recent years, evidence regarding their combined use in high-risk statin-intolerant patients remains limited. Furthermore, the pharmacokinetics of statins in toxic concentrations are poorly characterized in clinical settings. Case Presentation: We present two cases of genetically confirmed statin-induced rhabdomyolysis, both accompanied by severe acute kidney injury requiring renal replacement therapy. In both patients, serial measurements of rosuvastatin plasma concentrations revealed markedly delayed elimination, with detectable levels persisting for several weeks despite ongoing dialysis. Estimated half-lives exceeded 7 days in both cases, far beyond the known therapeutic range. Genetic testing identified SLCO1B1, ABCB1, and CYP2C9 polymorphisms linked to reduced hepatic uptake and impaired drug clearance. Following biochemical recovery, both patients were initiated on a triple non-statin lipid-lowering regimen consisting of ezetimibe, bempedoic acid, and inclisiran. The combination was well tolerated, with no recurrence of muscle-related symptoms or biochemical toxicity. LDL-C levels were reduced from 3.05 to 1.59 mmol/L and from 4.99 to 1.52 mmol/L, respectively, with sustained response over 12 and 40 weeks. Full lipid profiles demonstrated favorable changes across all parameters. Conclusions: These two cases suggest that the combination of ezetimibe, inclisiran, and bempedoic acid may serve as a safe and effective therapeutic option in patients with severe statin intolerance. Pharmacogenetic testing and serial pharmacokinetic assessment may guide personalized lipid-lowering strategies and improve outcomes in this challenging patient population. Full article

(This article belongs to the Topic Research in Pharmacological Therapies, 2nd Edition)

►▼ Show Figures

Graphical abstract

32 pages, 1496 KB  

Open AccessReview

Osteoporosis: Causes, Mechanisms, Treatment and Prevention: Role of Dietary Compounds

by Kristine Stromsnes, Cristian Martinez Fajardo, Silvana Soto-Rodriguez, Erika Ria Ulrika Kajander, Remus-Iulian Lupu, Monica Pozo-Rodriguez, Balma Boira-Nacher, Maria Font-Alberich, Marcos Gambini-Castell, Gloria Olaso-Gonzalez, Maria-Carmen Gomez-Cabrera and Juan Gambini

Pharmaceuticals 2024, 17(12), 1697; https://doi.org/10.3390/ph17121697 - 16 Dec 2024

Cited by 14 | Viewed by 11457

Abstract

Osteoporosis is a chronic disease that is characterized by a loss of bone density, which mainly affects the microstructure of the bones due to a decrease in bone mass, thereby making them more fragile and susceptible to fractures. Osteoporosis is currently considered one [...] Read more.

Osteoporosis is a chronic disease that is characterized by a loss of bone density, which mainly affects the microstructure of the bones due to a decrease in bone mass, thereby making them more fragile and susceptible to fractures. Osteoporosis is currently considered one of the pandemics of the 21st century, affecting around 200 million people. Its most serious consequence is an increased risk of bone fractures, thus making osteoporosis a major cause of disability and even premature death in the elderly. In this review, we discuss its causes, the biochemical mechanisms of bone regeneration, risk factors, pharmacological treatments, prevention and the effects of diet, focusing in this case on compounds present in a diet that could have palliative and preventive effects and could be used as concomitant treatments to drugs, which are and should always be the first option. It should be noted as a concluding remark that non-pharmacological treatments such as diet and exercise have, or should have, a relevant role in supporting pharmacology, which is the recommended prescription today, but we cannot ignore that they can have a great relevance in the treatment of this disease. Full article

(This article belongs to the Topic Research in Pharmacological Therapies, 2nd Edition)

►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less

Select all

Export citation of selected articles as:

Plain Text BibTeX BibTeX (without abstracts) Endnote Endnote (without abstracts) Tab-delimited RIS

 

Error

Oops... you haven't selected anything for export.

Ok

clear

Displaying articles 1-7