International comparison of generic competition, prices, and usage trends: South Korea and G20 countries.

Introduction: While many countries have successfully promoted generic drug use, South Korea faces challenges with low utilization and high expenditure shares, despite various policy reforms. This study aimed to evaluate the effectiveness of generic drug policies in South Korea, by comparing the prices, competition, and usage trends of generic drugs between South Korea and the Group of Twenty (G20) countries.

Methods: We analyzed 26 off-patent active ingredients marketed in South Korea and G20 countries from 2014 to 2023.

Development of 9-cinnamyl-9H-purine derivatives as potent anticancer agents through inactivation of NF-κb/p65 and p-STAT1 signaling pathways: Discovery of a new template for adenosine receptor.

Based on the structure of resveratrol and curcumin, a novel 9-cinnamyl-9H-purine structure was designed and synthesized to avoid a pan-assay interference compound (PAINS) related to invalid metabolic pancreas activity (IMPS). In a previous study, it exhibited anti-inflammatory activities by disrupting the TLR4-MyD88 protein interaction, leading to the suppression of the NF-κB signaling pathway. In this study, further structure-activity relationship studies were conducted to evaluate 9-cinnamyl-9H-purine derivatives for their potential anticancer activities, as NF-κB inhibition is known to reduce tumor growth and increase cancer cell death.

Discovery of a novel molecular glue degrader targeting GSPT1/2 with a non-IMiD-based CRBN binder.

Targeting undruggable proteins by inducing proximity between E3 ligase and their substrates has emerged as an innovative strategy for tackling challenging diseases. In this study, we identified a novel GSPT1 degrader, 4a (KMG-1068), through screening of our in-house small molecule library. Treatment with 4a demonstrated significant anti-proliferative activity across multiple cell lines, which was diminished by co-treatment with MLN4924, suggesting the involvement of the Cullin-containing complex.

Discovery of novel WRN inhibitors for treating MSI-H colorectal cancers.

The Werner protein, WRN, is a member of the RecQ helicase family implicated in genome maintenance. Several large-scale functional genomics screens have identified WRN as a synthetic lethal target in cancer cell lines with microsatellite instability-high (MSI-H). Accordingly, WRN is considered a potential therapeutic target in MSI-H cancers.

Prostate cancer-selective anticancer action of an oxindole derivative via HO-1-mediated disruption of metabolic reprogramming.

Prostate cancer, the second leading cause of cancer-related mortality in men, exhibits distinct metabolic reprogramming involving zinc and citrate metabolism. This study investigated whether targeting this unique metabolic profile could offer an effective therapeutic approach. A series of novel oxindole derivatives were synthesized and evaluated for their inhibitory effects on transcription factors (TFs) and antiproliferative activity across various cancer cell lines.

PRMT1-mediated methylation regulates MLL2 stability and gene expression.

The interplay between multiple transcription factors precisely regulates eukaryotic transcription. Here, we report that the protein methyltransferases, MLL2/KMT2B and PRMT1, interact directly and act collectively to regulate gene expression. PRMT1 binds to the N-terminal region of MLL2, considered an intrinsically disordered region, and methylates multiple arginine residues within its RGG/RG motifs.

Prognostic Efficacy of the Albumin-Bilirubin Score and Treatment Outcomes in Hepatocellular Carcinoma: A Large-Scale, Multi-Center Real-World Database Study.

Introduction: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, with treatment outcomes closely tied to liver function. This study evaluates the prognostic utility of the albumin-bilirubin (ALBI) score compared to the traditional Child-Pugh (CP) grading, leveraging real-world evidence from a large-scale, multi-center database.

Methods: The Liver Cancer IN Korea (LINK) research network, a multi-center initiative, retrospectively collected electronic health records from three academic hospitals in South Korea, encompassing HCC patients diagnosed between 2015 and 2020.

Design and evaluation of anaplastic lymphoma kinase degraders using a covalent fumarate handle.

Targeted protein degradation has emerged as a novel therapeutic paradigm in drug discovery. Despite the FDA approval of anaplastic lymphoma kinase (ALK) inhibitors, the pursuit of compounds with enhanced potency and prolonged efficacy remains crucial to mitigate inevitable adverse effects. In this context, we endeavored to develop ALK degraders utilizing FDA-approved ALK inhibitors-crizotinib, ceritinib, brigatinib, and alectinib-as ALK binders, along with 4-methoxyphenylfumarate as a covalent handle to bind to RNF126 E3 ligase.

Comparing Costs and Healthcare Resource Utilization (HCRU) Using LAMA versus LABA/ICS at Treatment Initiation for COPD: Findings from CITRUS (Comparing the Incidence of Tiotropium and ICS/LABA in Real-World Use in South Korea) Study.

Background: COPD causes substantial economic burden on healthcare. Alternative treatment strategies for COPD can be associated with different costs dependent upon their relative safety and effectiveness. We compared costs and healthcare resource utilization (HCRU) associated with LAMA or LABA/ICS initiation.

G Protein-Coupled Estrogen Receptor-Mediated Anti-Inflammatory and Mucosal Healing Activity of a Trimethylpyridinol Analogue in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is characterized by abnormal immune responses, including elevated proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in the gastrointestinal (GI) tract. This study presents the synthesis and anti-inflammatory evaluation of 2,4,5-trimethylpyridin-3-ol analogues, which exhibit dual inhibition of TNFα- and IL-6-induced inflammation. Analysis using methods, including 3D shape-based target identification, modeling, and docking, identified G protein-coupled estrogen receptor 1 (GPER) as the molecular target for the most effective analogue, -, which exhibits remarkable efficacy in ameliorating inflammation and restoring colonic mucosal integrity.

siRNA treatment targeting integrin α11 overexpressed via EZH2-driven axis inhibits drug-resistant breast cancer progression.

Background: Breast cancer, the most prevalent cancer in women worldwide, faces treatment challenges due to drug resistance, posing a serious threat to patient survival. The present study aimed to identify the key molecules that drive drug resistance and aggressiveness in breast cancer cells and validate them as therapeutic targets.

Methods: Transcriptome microarray and analysis using PANTHER pathway and StemChecker were performed to identify the most significantly expressed genes in tamoxifen-resistant and adriamycin-resistant MCF-7 breast cancer cells.

Treatment compliance, treatment patterns, and healthcare utilization in epilepsy patients with first add-on antiepileptic drugs: A nationwide cohort study.

Objective: This study aimed to assess the treatment compliance, patterns, healthcare resource utilization (HCRU), and costs of anti-epilepsy drugs (AEDs) as the first add-on therapy in patients with epilepsy.

Methods: We conducted a retrospective population-based cohort study using Korean National Health Insurance claims data from 2016 to 2020. Patients with epilepsy who newly received AED add-on therapy were identified and followed for up to 12 months to evaluate persistence, adherence, treatment patterns, HCRU, and costs.

Complete genome sequence of CACC 537 isolated from canine.

CACC 537 was isolated from canine feces and reported to have probiotic properties. We aimed to characterize the potential probiotic properties of this strain by functional genomic analysis. Complete genome sequencing of CACC 537 was performed using a PacBio RSII and Illumina platform, and contained one circular chromosome (2.

Hypoxia stabilizes SETDB1 to maintain genome stability.

Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target.

Life expectancy and healthy life expectancy of Korean registered disabled by disability type in 2014-2018: Korea National Rehabilitation Center database.

Background: Conducting a distinct comparison between the life expectancy (LE) and healthy life expectancy (HALE) of people with disabilities (PWDs) and the general population is necessary due to the various environmental and health conditions they encounter. Therefore, this study aimed to develop the life table for PWDs and calculate those of LE and HALE based on sex, severity, and disability types among the registered Korean PWDs.

Methods: We used aggregated data of registered PWDs from the Korea National Rehabilitation Center database between 2014 and 2018.

Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample.

Objectives: We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea.

Methods: In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics.

Complete genome sequence of functional probiotic candidate CACC736.

CACC736 was originated from swine feces in Korea. The complete genome sequences of the strain contained one circular chromosome (2,057,809 base pair [bp]) with 38.2% guanine-cytosine (GC) content and two circular plasmids, namely, pCACC736-1 and pCACC736-2.