The discovery of a novel series of cyclopenta[b]furans as CCR2 inhibitors is discussed. This series has excellent CCR2 potency and PK characteristics, and good cardiovascular safety.
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http://dx.doi.org/10.1016/j.bmcl.2014.03.036 | DOI Listing |
RSC Med Chem
January 2025
Department of Chemistry, The State University of New York at Buffalo Natural Sciences Complex Buffalo NY 14260 USA
Small molecules targeting activating mutations within the epidermal growth factor receptor (EGFR) are efficacious anticancer agents, particularly in non-small cell lung cancer (NSCLC). Among these, lazertinib, a third-generation tyrosine kinase inhibitor (TKI), has recently gained FDA approval for use in combination with amivantamab, a dual EGFR/MET-targeting monoclonal antibody. This review delves into the discovery and development of lazertinib underscoring the improvements in medicinal chemistry properties, especially in comparison with osimertinib.
View Article and Find Full Text PDFJ Med Chem
January 2025
School of Pharmaceutical Sciences, University of Geneva, 1206 Geneva, Switzerland.
Inhibition of the adenosine 2A receptor (AR) is recognized as a promising immunotherapeutic strategy but is challenged by the ubiquity of AR function in the immune system. To develop a safe yet efficacious immunotherapy, the discovery of a novel negative allosteric modulator (NAM) was preferred. Leveraging an in-house, sensitive, high-throughput screening cellular assay, novel AR NAM scaffolds were identified, followed by an extensive structure-activity relationship (SAR) study, leading to the discovery of potent 2-amino-3,5-dicyanopyridine derivatives.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China. Electronic address:
Melanoma is characterized by its aggressiveness, high metastatic potential, and numerous mutations, which limit the effectiveness of current treatments. To address this issue, we developed a dissolvable microneedle (MN) system composed of poly(2-ethyl-2-oxazoline) (PEtOz) and chondroitin sulfate (CS). This MN system was loaded with liposomes containing both a NIR-II photothermal small molecule (IRLy) and the natural anticancer agent Gambogic acid (GA), forming Lip(IRLy + GA) MNs.
View Article and Find Full Text PDFAnnu Rev Pathol
January 2025
MASLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA; email:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem, affecting ∼1 billion people. This condition is well established to have a heritable component with strong familial clustering. With the extraordinary breakthroughs in genetic research techniques coupled with their application to large-scale biobanks, the field of genetics in MASLD has expanded rapidly.
View Article and Find Full Text PDFCells
January 2025
Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
Alpha-1 antitrypsin (AAT) is a key serine protease inhibitor for regulating proteases such as neutrophil elastase. AAT restrains the pulmonary matrix from enzymatic degradation, and a deficiency in AAT leads to inflammatory tissue damage in the lungs, resulting in chronic obstructive pulmonary disease. Due to the crucial biological function of AAT, the emerging research interest in this protein has shifted to its role in cancer-associated inflammation and the dynamics of the tumor microenvironment.
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