Current Topics in Medicinal Chemistry - Online First

The goal of this study is to provide a comprehensive review of physicochemical and pharmacological properties, including pharmacokinetics and pharmacodynamics parameters, with an overview of preclinical and clinical trial data, chemistry, and multiple routes of synthesis, bioanalytical methods, and patents of the API: Vadadustat

A review was conducted by compiling data from Science Direct, PubMed, Drug Bank, WIPO patent, Clinicaltrialgov, Wolters Kluwer, and many others to enhance understanding of the topic

The FDA approved Vadadustat on March 27, 2024, for treating anemia in adults with CKD on dialysis. Vadadustat effectively increased hemoglobin levels in both non-dialysis and dialysis-dependent CKD patients. It showed comparable efficacy to traditional erythropoiesis-stimulating agents (ESAs) like darbepoetin alfa. Multiple clinical trials, including Phase 2 and Phase 3 studies, demonstrated Vadadustat’s potential as an effective treatment for anemia in CKD patients.

Vadadustat, as an oral HIF-PH inhibitor, offers significant advantages in the treatment of anemia in CKD. Its oral route of administration improves patient compliance, and its efficacy is comparable to ESAs. Clinical and preclinical data support its safety and therapeutic potential, although long-term cardiovascular effects remain under observation.

This review examines therapeutic, pharmacological, analytical, and regulatory aspects related to Vadadustat.

The limitations of conventional drug delivery methods, such as systemic side effects and poor absorption, highlight the need for safer and more effective alternatives. Polysaccharides, due to their biocompatible, biodegradable, and mucoadhesive properties, have shown promise in formulations for the oral cavity, particularly in localized delivery systems and tissue regeneration. This study aims to conduct a bibliometric analysis to characterize the scientific output on the use of polysaccharides in the oral cavity, identifying trends, international collaborations, and research gaps.

A Web of Science search was conducted in January 2025 using keywords related to polysaccharides and mucosal adhesion. The analysis included original articles published in English between 2015 and 2024. Bibliometric data and study characteristics were extracted and analyzed, focusing on study types, formulation types, and international collaborations.

The analysis included 66 articles with 1144 citations. In vitro studies were predominant, while clinical trials were lacking. Chitosan and alginate emerged as the most commonly used polysaccharides, with gels and hydrogels being the most prevalent formulations. International collaborations involved 28 countries, with China, Brazil, and Italy standing out in terms of scientific production.

The results highlight important advancements in the use of polysaccharides for oral cavity formulations, particularly in gels and hydrogels. However, the predominance of in vitro studies and the lack of clinical trials suggest limitations for translating these findings into clinical practice. The strong performance of countries such as China, Brazil, Italy, Spain, and Norway underscores the relevance of international collaborations and the global potential of this topic.

The increasing scientific output reflects the growing interest in the use of polysaccharides for oral health applications. Despite these advancements, critical gaps remain, such as the lack of clinical studies. Future research should prioritize translational studies, personalized therapies, and the sustainable development of biomaterials.

Cancer remains a devastating global health burden. Despite the identification of numerous biological targets, effective therapeutic agents remain limited. As a highly promising novel target, the role of Discoid Domain Receptors (DDRs) in pan-cancer biology is still poorly characterized. Thus, this study aims to elucidate the regulatory mechanisms and diagnostic potential of DDR1 across different cancer types.

Herein, we used UCSC, SangerBox, GEPIA, GSCA, and GeneMANIA online databases to analyze the expression and role of DDR1 in pan-cancer.

The expression levels of DDR1 showed significant differences in some tumour T, N, and M stages. Importantly, DDR1 expression was associated with clinical prognosis in five cancers. In addition, DDR1 was inversely correlated with most immune checkpoint pathways, immunomodulatory genes, and immune cell infiltration in a few cancers. Furthermore, in most cancers, DDR1 promotes cancer progression by promoting apoptosis, inhibiting cell cycle and EMT, activating hormone AR activity, activating PI3K/AKT pathway, RASMAPK pathway, and RTK pathway. Finally, we also found that the DDR1 gene was positively associated with stemness scores in most tumors.

Our findings demonstrate that DDR1 exhibits diagnostic utility and holds promising translational potential as a therapeutic target across multiple cancer types.

Many metabolic diseases, such as Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), are largely caused by obesity, a complicated ailment characterized by excessive fat buildup. By 2030, obesity is expected to have increased in prevalence, affecting over 1 billion people worldwide. MASLD, formerly known as NAFLD, is a broad category of liver illnesses caused by metabolic dysfunction and frequently linked to obesity. Drugs are available for obesity, but long-term use causes serious adverse effects, as reported. Currently, there are no FDA-approved therapies for MASLD. Interest in marine animals and their metabolites for their potential as therapeutics is growing, given the shortcomings of traditional medicines. This review emphasizes different marine species and metabolites, and macromolecules and tabulates all the pre-clinical studies targeting obesity and MASLD.

For this review, the authors have gone through a vast number of article sources from different scientific databases like PubMed, Google Scholar and ScienceDirect.

Algae, fungi, and bacteria found in the ocean are abundant in bioactive chemicals that have anti-obesity and anti-MASLD properties. A variety of studies have reported the anti-obesity and anti-MASLD effects of marine species such as Spirulina platensis, Chlorella vulgaris, Caulerpa okamurae, and bioactive macromolecules like dieckol, fucosterol, fucoxanthin, sodium alginate and paramylon.

These marine-derived substances have a variety of pharmacological characteristics, including lipid-modulating, anti-adipogenic, antioxidant, and anti-inflammatory activities. These qualities are crucial for treating the underlying mechanisms that underlie obesity and MASLD. These marine species may be useful as natural supplements or therapeutic agents in the management and treatment of metabolic diseases associated with obesity. Some of these bioactive phytoconstituents have been identified for their potential against obesity and MASLD; however, more investigation is necessary to identify the precise bioactive substances causing these advantageous effects and assess their safety and effectiveness in clinical trials.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. M1 macrophages exhibit dual roles in the tumor microenvironment (TME), but the specific mechanisms underlying their involvement in HCC remain unclear.

M1-polarized macrophages were differentiated from THP-1 monocytes employing Phorbol 12-Myristate 13-Acetate (PMA) and lipopolysaccharide (LPS). Then, macrophage activity was determined based on Mean Fluorescence Intensity (MFI), and their metabolic capacity was assessed according to extracellular acidification rate (ECAR) and Oxygen Consumption Rate (OCR). Quantitative Real-Time PCR (qRT-PCR) was performed to assess the expression of polarization-related genes.

The results showed that LPS at a concentration higher than 10 ng/mL significantly affected the viability of macrophages differentiated from THP-1 monocytes but promoted the MFI of CD86. At the same time, LPS treatment notably enhanced the M1 polarization of macrophages, as evidenced by the upregulated expression of markers related to the M1 phenotype. Moreover, the mitochondrial oxidative metabolism of M1 macrophages shifted toward aerobic glycolysis under LPS treatment. When T-cells and HCC cells were co-cultured with M1 macrophages, the reactivity of T cells was enhanced, and the level of Bax (an apoptosis-enhancer) was increased. At the same time, the expression of Bcl-2 (an apoptosis-suppressor) was suppressed.

LPS-induced M1 macrophages exert antitumor effects through metabolic reprogramming and immune modulation, though further mechanistic studies are needed.

M1 macrophages inhibit HCC progression by activating T cells and inducing tumor cell apoptosis, offering novel insights for HCC immunotherapy.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are one of the most widely prescribed medications in the world, yet their applications as anti-inflammatory, analgesic, and anti-pyretic drugs remain principally restricted by their detrimental effects on the gastrointestinal tract (GIT) systems. The prodrug approaches have substantially combated the drawbacks of currently available marketed NSAIDs and also showed increased activity.

In the present study, an extensive literature review on mutual prodrugs of NSAIDs with natural antioxidants has been presented.

Different databases like ScienceDirect, Elsevier, PubMed, Google Scholar, etc. were used for an extensive search of articles related to NSAIDs, prodrug concepts, as well as research based on all of the NSAIDs-prodrug molecules prepared to date.

Recent developments in prodrug design have been explored that utilize naturally occurring antioxidants, including Thymol, Guaiacol, Menthol, Eugenol, Sesamol, Vanillin, and Umbelliferon, for the synthesis of mutual prodrugs by esterification methods. Many studies have shown that these prodrugs have significant stability in acidic pH while hydrolyzing in neutral and alkaline pH environments. This indicates their potential as advantageous therapeutic agents with enhanced safety profiles.

The mutual prodrug strategy offers a chance in medicinal chemistry to enhance the therapeutic and clinical efficiency of a drug that has certain unfavorable qualities that limit its clinical utility. This review enlightens mutual prodrugs of NSAIDs and antioxidants that are less harmful and beneficial to mankind, respectively.

Myocyte enhancer factor 2C (MEF2C) is a pivotal transcription factor that is responsible for maintaining myocyte differentiation. MEF2C is multifunctional, participating in diverse biological processes, including cardiac morphogenesis, angiogenesis, neurogenesis, and cortical development. Emerging evidence has identified MEF2C as a novel oncogene with dual regulatory functions in tumorigenesis. However, the mechanisms by which MEF2C regulates the progression of various malignant tumors are unknown. Therefore, it is crucial to further investigate the multiple signaling pathways under different expression levels of MEF2C. In this review, the expression level of MEF2C in various malignant tumors and its specific pathways are described.

This review systematically summarizes and critically analyzes the current studies on MEF2C’s biological function in malignant tumors by comprehensively searching them in PubMed databases.

MEF2C demonstrates aberrant expression patterns across multiple tumor types, spanning both solid tumors (e.g., glioma, breast cancer, hepatocellular carcinoma) and hematological malignancies (e.g., leukemia). MEF2C orchestrates multiple oncogenic processes, including tumor cell proliferation, migration, and invasion, while also modulating cancer drug resistance and systemic manifestations, like cachexia and apoptosis resistance.

Given its multifaceted roles in tumor initiation, progression, and clinical aspects, MEF2C has the potential to serve as both a diagnostic biomarker and a therapeutic target for various malignancies.