Epalrestat is the only aldose reductase inhibitor that is currently available for diabetic peripheral neuropathy. Oxidative stress impairs endothelial cells, thereby leading to numerous pathological conditions. Increasing antioxidative ability is important to prevent cellular toxicity induced by reactive oxygen species. Epalrestat increases antioxidant defense factors such as glutathione and γ-glutamylcysteine ligase in vascular endothelial cells through activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). This increases suppression of oxidative stress-induced cellular toxicity. Cadmium is an industrial and environmental pollutant that targets the vascular endothelium. The vascular system is critically affected by cadmium toxicity. Therapeutic treatment against cadmium toxicity is chelation therapy that promotes metal excretion; however, cadmium chelators can cause renal toxicity. Therefore, safe and efficient therapeutic agents are required. Epalrestat suppresses cadmium-induced cytotoxicity in vascular endothelial cells through activation of Nrf2. In addition, epalrestat affects the intracellular levels of cadmium, cadmium transporter Zrt-Irt-like protein 8 (ZIP8), and metallothionein (MT). The upregulation of ZIP8 and MT may be involved in the suppression of cadmium-induced cytotoxicity by epalrestat. Drug repurposing is a new strategy for drug discovery in which the pharmacological action of existing medicines whose safety and pharmacokinetics have already been confirmed clinically and whose use has been approved is examined comprehensively at the molecular level. The results can be applied to the development of existing drugs for use as medicines for the treatment of other diseases. This review provides useful findings for future expansion of indications as research leading to drug repurposing of epalrestat.

Sialic acid-binding lectin from Rana catesbeiana (cSBL) is a multifunctional protein with both lectin and ribonuclease activity and is, therefore, called a leczyme. It exerts cancer cell-selective antitumor effects on a variety of cancer cells in vitro and in vivo under conditions where no undesired side effects are observed. cSBL elicits antitumor effects by degrading cellular RNA and subsequently inducing apoptosis via a pathway mediated by mitochondria and endoplasmic reticulum stress. Further, it exerts synergistic antitumor effects with other molecules such as tumor necrosis factor-related apoptosis-inducing ligand and pemetrexed. Recent studies have revealed that long-term treatment of cancer cells with cSBL causes significant pleiotropic changes in the expression profiles of several genes, including multiple genes involved in metabolic pathways. Furthermore, cSBL reduces the expression of some cancer-related molecules such as human epidermal growth factor receptors, aldo-keto reductase 1B10, and ATP-binding cassette transporter C2. The information described above is expected to lead to useful applications, such as effective regimens comprising cSBL and other drugs. These findings reveal favorable properties of cSBL as an anticancer drug, which may contribute to the development of new therapeutic strategies for cancer treatment.

As intermolecular and intramolecular disulfide bridges in proteins play a vital role in the stability of the final protein structure, the disruption of disulfide bridges in proteins may lead to disease development and progression. Therefore, understanding the association of abnormal protein disulfide bond formation with disease development and progression can be useful for developing novel drugs for various diseases. Considering that disulfide-linked protein folding involves redox reactions in the endoplasmic reticulum, this process may be affected by oxidative stress. We hypothesized that oxidative stress-related diseases may be induced by abnormal protein disulfide bond formation. This review introduces the association of abnormal protein disulfide bond formation with disease development and progression.

Medium-sized peptides are expected as a next-generation drug discovery modality because they combine the properties of conventional small-molecule drugs and biopharmaceuticals. Nonetheless, peptides are easily degraded by digestive enzymes such as protease in the body, which could be problematic for the development of peptide-based drugs. To overcome such a problem, peptide-based foldamers containing non-proteinogenic amino acids or cyclized peptides have been reported. In addition, peptides must form stable secondary structures and their side chains should be correctly positioned to exert their bioactivity. In our lab, bioactive peptides have been developed based on regulation of secondary structures by introducing non-proteinogenic amino acids such as acyclic α,α-disubstituted amino acids (dAAs), cyclic dAAs, cyclic β-amino acids, and side-chain stapling. Based on these knowledges, I have been performing research on the development of bioactive peptides based on the secondary structural control of peptides as categorized in the following manner: (1) rational design of antimicrobial foldamers; (2) post-functionalization of helical peptides; (3) development of carrier peptides for intracellular delivery of siRNA utilizing the helical template peptides.

Research on natural product chemistry via organic chemistry ranges from isolation and structural elucidation to total synthesis, drug discovery, and chemical biology. Discoveries in organic chemistry, such as novel reactions and synthetic strategies, are enabled by the studies of total synthesis. Thus, organic (synthetic) chemistry and natural product chemistry are correlated. We conducted comprehensive studies, including structure-activity relationship, drug discovery, and total synthesis studies, on the synthetic organic chemistry of natural products with unique biological activities and the development of novel reactions discovered through these products. This review describes the total synthesis of simpotentin, a novel potentiator of amphotericin B, and the development of the novel lactonization reactions of homopropargyl alcohols via intramolecular ketene trapping.

As the term polypharmacology suggests, there are multiple actions of small-molecule compounds. We proposed a decomposition and understanding concept that sheds light on the small effects in comparison to the large effects by decomposing these multiple effects. This concept was embodied by describing the effects of the compounds in a transcriptome profile, followed by factor analysis to extract latent variables as decomposed effects. Application of this approach to public datasets resulted in the inferences of compound effects consistent with existing knowledge such as gene ontologies and pathways. In one experimental validation, the potential inducibility of endoplasmic reticulum stress of several commercial drugs was detected by decomposition. Another study successfully discriminated the effects of a natural product and its derivatives despite their structural similarity. In the era of big data, it is important to infer conceptual elements composed of measurable elements as a higher layer than the given data of a specimen, which can expand our perception and understanding of the specimen. This review introduces an example of such a philosophy by applying it to the multiple effects of drugs to contribute to the understanding.

Glycans are present in all living organisms, including viruses, bacteria, and animals, and perform various biological functions. The author has been studying influenza viruses' glycan usage mechanisms, particularly the functional analysis of neuraminidase (NA), a viral sialidase. The authors recently focused on influenza virus NAs' high sialidase activity with the aim of using sialidase activity detection as a virus detection technology. Using the probe BTP3-Neu5Ac, allows fluorescent imaging of sialidase activity, we created a new technique for easy, rapid, and high sensitivity fluorescent imaging of virus-infected cells. The detection of viruses using BTP3-Neu5Ac does not require specific antibodies and can be performed by simply adding reagents. Furthermore, fluorescence imaging of sialidase as a virus detection technology has many advantages, including isolating viruses from fluorescently imaged infected cells. This detection technique is easy to use in basic research and hygiene testing, where viral culture is conducted and is expected to be widely used.

It is well-established that G protein-coupled receptors (GPCRs) transduce signals into cells using G proteins as intermediary molecules. β-Arrestins are molecules involved in regulating GPCRs; however, it has recently been reported that β-arrestins can also mediate signaling through GPCRs. Signaling through G proteins or β-arrestins can be activated selectively using specific agonists; of the latter, those that can selectively activate either G proteins or β-arrestins are called biased agonists. The clinical use of biased agonists could potentially induce fewer side effects. However, partial agonists can also explain the mechanism of G protein-biased agonists; thus, appropriate assay systems must be considered. Endogenous agonists are known to bind to orthosteric and allosteric sites in the agonist binding site, and the allosteric site is associated with the activity of biased agonists. This current review presents a detailed discussion of biased agonists.

Collaborations between hospital and community pharmacists play a key role in ensuring consistent continuation of pharmacotherapy within official medical care plans designed to promote community-based healthcare. A previous study conducted by the authors clarified the constructs of collaboration between the hospital and community pharmacists from the hospital pharmacist's perspective. In this study, a similar questionnaire was used to survey a group of pharmacies with 424 outlets nationwide, and 244 responses were collected. Factor analysis from the community pharmacists' perspective extracted five latent factors comprising 18 variables, and structural equation modeling yielded a model with a high goodness-of-fit. In the latter model, variables representing “Organizational climate” and “Basic policy on collaboration” formed the foundation of the collaboration between hospital and community pharmacists, while variables representing “Understanding of healthcare policy”, “Resources for collaboration”, and “Community support systems” represented concepts that flexibly compensated for fluctuations in medical policy. These trends were similar to those of the constructs previously indicated by hospital pharmacists. We performed multiple regression analysis and structural equation modeling to confirm the impact of the inclusion of “Need for collaboration” as a dependent variable on the proposed constructs of hospital-community pharmacist collaboration using different analytical methods. Our results indicated that “Organizational climate”, “Basic policy on collaboration”, and “Community support systems” affected the “Need for collaboration”. Our findings indicate that future studies are needed to confirm and clarify the causal relationships demonstrated by the constructs of hospital-community pharmacist collaboration seen within the current study.

There is a need for pharmacists to be actively involved in home healthcare through a wide range of collaboration in healthcare and welfare. However, insufficient evidence is available to search for factors that prevent pharmacists from being proactive in home healthcare. In this study, we conducted an extensive questionnaire survey among pharmacists engaged in home pharmacy work who belong to the Hyogo Pharmaceutical Society regarding the current status of pharmacists' work in home medical care and their psychological burden; we also explored the factors that may hinder the future development of home medical care. As a result, 925 (44%) valid responses were obtained, and seven factors— “current multidisciplinary cooperation”, “relationships with patients and their families”, “emotional burden for home healthcare”, “attitude toward patients”, “ideal of multidisciplinary cooperation”, “anxiety about aggressive intervention”, and “anxiety about talking to and dealing with patients”— were extracted. Furthermore, it was suggested that pharmacists' mental burden and anxiety are closely related to their successful experiences in building relationships with patients and patients' families as well as with multidisciplinary cooperation in home healthcare. Therefore, to train pharmacists to be actively involved in home healthcare, it is important not only to impart knowledge and skills but also for them to gain experience practicing their contributions as pharmacists in the field of home healthcare with multiple professions, patients, and patients' families.

A 55-year-old man with hypertrophic cardiomyopathy and a pacemaker was admitted with coronavirus disease 2019 (COVID-19). Before admission, the patient's medications included amiodarone, diltiazem, bisoprolol, atorvastatin, etizolam, and warfarin (WF). After admission, dexamethasone (DXM) and remdesivir (RDV) were initiated for treating COVID-19. The international normalized ratio (INR) on admission was 1.8, which increased to 3.4 on day 5 and to 6.9 on day 10 after admission. Although there have been reports that RDV may occasionally prolong prothrombin time and that the degree of prolongation is often less severe, the mechanism of action has not been elucidated till date. There are reports of prolonged INR when WF is co-administered with RDV and DXM, suggesting that drug interactions may be a potential cause for the prolongation. A similar drug interaction may have potentially occurred in the case reported here. In addition, this case used amiodarone (AMD), and it has been reported that the RDV concentration increases when used in combination with AMD. Further investigations are needed to elucidate the cause of INR prolongation. Thus, close monitoring of the patient is recommended when RDV is co-administered with high-risk agents to avoid unnecessary side effects.