Selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have considerable potential as treatment for osteoporosis as well as metabolic syndrome including type 2 diabetes mellitus. Here, we investigated the anti-diabetic, anti-adipogenic, and anti-osteoporotic activity of KR-67500, as a novel selective 11β-HSD1 inhibitor. Cellular 11β-HSD1 activity was tested based on a homogeneous time-resolved fluorescence method. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) levels were measured in diet-induced obese (DIO)-C57BL/6 mice administered KR-67500 (50 mg/kg per day, p.o.) for 28 days and, additionally, its anti-diabetic effect was evaluated by OGTT and ITT. The in vitro anti-adipogenic effect of KR-67500 was determined by Oil Red O Staining. The in vitro anti-osteoporotic activity of KR-67500 was evaluated using bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation model systems. KR-67500 improved the in vivo glucose tolerance and insulin sensitivity in DIO-C57BL/6 mice. KR-67500 suppressed cortisone-induced differentiation of 3T3-L1 cells into adipocytes. KR-67500 enhanced BMP2-induced osteoblastogenesis in C2C12 cells and inhibited RANKL-induced osteoclastogenesis in mouse bone marrow-derived macrophages. KR-67500, a new selective 11β-HSD1 inhibitor, may provide a new therapeutic window in the prevention and/or treatment of type 2 diabetes, obesity, and/or osteoporosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1530/JME-13-0177 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Virtual screening of potential inhibitors of the ATPase site in Acinetobacter baumannii DNA Gyrase.
Comput Biol Med
January 2025
Laboratorio de Fisicoquímica Analítica, Unidad de Investigación Multidisciplinaria, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Cuautitlán Izcalli, Estado de México, 54714, Mexico. Electronic address:
Bacterial resistance is a global public health problem because of the ineffectiveness of conventional antibiotics against super pathogens. To counter this situation, the search for or design of new molecules is essential to inhibit the key proteins involved in several stages of bacterial infection. One of these key proteins is DNA gyrase, which is responsible for packaging and unfolding of DNA chains during replication.
View Article and Find Full Text PDFD-glucose-conjugated thioureas containing 2-aminopyrimidine as potential multitarget inhibitors for type 2 diabetes mellitus: Synthesis and biological activity study.
Comput Biol Med
January 2025
Faculty of Chemistry, University of Science (Vietnam National University, Hanoi), 19 Le Thanh Tong, Hoan Kiem, Ha Noi, Viet Nam; VNU University of Education, Vietnam National University, Hanoi, 144 Xuan Thuy, Cau Giay, Ha Noi, Viet Nam.
α-d-Glucose-conjugated thioureas 8a-w of substituted 4,6-diaryl-2-aminopyrimindines were designed, synthesized, and screened for their antidiabetic inhibitory activity. The thioureas with the strongest potential inhibitory activity included 8f (IC = 11.32 ± 0.
View Article and Find Full Text PDFPopulation pharmacokinetics of erlotinib in patients with non-small cell lung cancer (NSCLC): A model-based meta-analysis.
Comput Biol Med
January 2025
Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; Department of Pharmaceutical Medicine and Regulatory Science, Yonsei University, Incheon, Republic of Korea; Graduate Program of Industrial Pharmaceutical Science, Yonsei University, Incheon, Republic of Korea; Department of Integrative Biotechnology, Yonsei University, Incheon, Republic of Korea. Electronic address:
Background: Erlotinib is a potent first-generation epidermal growth factor receptor tyrosine kinase inhibitor. Due to its proximity to the upper limit of tolerability, dose adjustments are often necessary to manage potential adverse reactions resulting from its pharmacokinetic (PK) variability.
Methods: Population PK studies of erlotinib were identified using PubMed databases.
Comparison of tegoprazan and proton pump inhibitors for first-line eradication: a systematic review with meta-analysis.
Expert Rev Anti Infect Ther
January 2025
Department of Medical Biostatistics, Soonchunhyang University Hospital, Seoul, Korea.
Background: Tegoprazan (TPZ), a potassium-competitive acid blocker with potent gastric acid-suppressing activity, may be a potential agent for treating Helicobacter pylori infection. The study aimed to evaluate the efficacy of TPZ-based therapy for H. pylori eradication compared with proton pump inhibitor (PPI)-based therapy.
View Article and Find Full Text PDFPhosphodiesterase inhibition restoreshypoxia-induced cerebrovascular dysfunction subsequent to improved systemic redox homeostasis: A randomized, double-blind, placebo-controlled crossover study.
J Cereb Blood Flow Metab
January 2025
Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK.
To what extent sildenafil, a selective inhibitor of the type-5 phosphodiesterase modulates systemic redox status and cerebrovascular function during acute exposure to hypoxia remains unknown. To address this, 12 healthy males (aged 24 ± 3 y) participated in a randomized, placebo-controlled crossover study involving exposure to both normoxia and acute (60 min) hypoxia (Fi = 0.14), followed by oral administration of 50 mg sildenafil and placebo (double-blinded).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!