We designed and synthesized a novel class of dual pharmacology bronchodilators targeting both β(2)-adrenoceptor and PDE4 by applying a multivalent approach. The most potent dual pharmacology molecule, compound 29, possessed good inhibitory activity on PDE4B2 (IC(50)=0.278 μM, which was more potent than phthalazinone, IC(50)=0.520 μM) and possessed excellent relaxant effects on tracheal rings precontracted by histamine (pEC(50)=9.3).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2012.01.013 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Pharmacokinetic/Pharmacodynamic Study of Esomeprazole Comparing a Dual Delayed-Release Formulation (YYD601) to a Conventional Formulation Following Multiple Administrations in Healthy Adult Subjects.
Drug Des Devel Ther
January 2025
School of Medicine, Kyungpook National University and Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
Background: YYD601 is a new dual delayed-release formulation of esomeprazole, developed to enhance plasma exposure and prolong the duration of acid suppression.
Purpose: This study aimed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of YYD601 20 mg following single and multiple oral administrations in healthy, fasting adult Koreans, and to compare these outcomes to those of the conventional esomeprazole 20 mg capsule.
Methods: A randomized, open-label, two-period crossover study was conducted in 28 participants, who were divided into two treatment groups: one group received YYD601 20 mg, and the other received conventional esomeprazole 20 mg, once daily for five consecutive days.
Scutellarein Inhibits Osteosarcoma Growth by Targeting the TLR4/TRAF6/NF-κB Pathway.
Drug Des Devel Ther
January 2025
Department of Trauma Orthopedics, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272007, People's Republic of China.
Purpose: Osteosarcoma (OS) is the most common malignant tumor associated with poor patient outcomes and a limited availability of therapeutic agents. Scutellarein (SCU) is a monomeric flavone bioactive compound with potent anti-cancer activity. However, the effects and mechanisms of SCU on the growth of OS remain unknown.
View Article and Find Full Text PDFEngineered Perfluorochemical Cancer-Derived Exosomes Loaded with Indocyanine Green and Camptothecin Provide Targeted Photochemotherapy for Effective Cancer Treatment.
Int J Nanomedicine
January 2025
Department of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan, Republic of China.
Background: Cancer treatments are still limited by various challenges, such as off-target drug delivery, posttreatment inflammation, and the hypoxic conditions in the tumor microenvironment; thus, the development of effective therapeutics remains highly desirable. Exosomes are extracellular vesicles with a size of 30-200 nm that have been widely applied as drug carriers over the last decade. In this study, melanoma-derived exosomes were used to develop a perfluorocarbon (PFC) drug nanocarriers loaded with indocyanine green (ICG) and camptothecin (CPT) (ICFESs) for targeted cancer photochemotherapy.
View Article and Find Full Text PDFDrug-Linker Constructs Bearing Unique Dual-Mechanism Tubulin Binding Payloads Tethered through Cleavable and Non-Cleavable Linkers.
Tetrahedron
February 2025
Department of Chemistry and Biochemistry, Baylor University, One Bear Place, No. 97348, Waco, Texas 76798-7348, United States.
Antibody-drug conjugates (ADCs) have advanced as a mainstay among the most promising cancer therapeutics, offering enhanced antigen targeting and encompassing wide diversity in their linker and payload components. Small-molecule inhibitors of tubulin polymerization have found success as payloads in FDA approved ADCs and represent further promise in next-generation, pre-clinical and developmental ADCs. Unique dual-mechanism payloads (previously designed and synthesized in our laboratories) function as both potent antiproliferative agents and promising vascular disrupting agents capable of imparting selective and effective damage to tumor-associated microvessels.
View Article and Find Full Text PDFDesign, synthesis, and evaluation of dehydroabietyl imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones as TDP1 inhibitors and dual TDP1/TDP2 inhibitors.
Arch Pharm (Weinheim)
January 2025
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, Novosibirsk, Russian Federation.
Tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes involved in the repair of DNA, are regarded as promising targets for the development of new anticancer drugs. In this study, a series of imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones based on dehydroabietylamine (DHAAm) were synthesized. The inhibitory activity of the new compounds against TDP1 and TDP2, as well as their cytotoxic characteristics, were evaluated.
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!