A series of potent, selective inhibitors of protein kinase C has been derived from the structural lead provided by the microbial broth products, staurosporine and K252a. Our inhibitors block PCK in intact cells (platelets and T cells), and prevent the proliferation of mononuclear cells in response to interleukin 2 (IL2).
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http://dx.doi.org/10.1016/0014-5793(89)81494-2 | DOI Listing |
J Med Chem
January 2025
College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.
The P2YR is activated by UDP and UDP glucose and is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2YR antagonists and the crystallographic overlap study between PPTN and compound , a series of 3-substituted 5-amidobenzoate derivatives were designed, synthesized, and identified as promising P2YR antagonists. The optimal compound (methyl 3-(1-benzo[]imidazol-2-yl)-5-(2-(-tolyl) acetamido)benzoate, IC = 0.
View Article and Find Full Text PDFThe rise of drug-resistant fungal pathogens, including , highlights the urgent need for novel antifungal therapies. We developed a cost-effective platform combining microbial extract prefractionation with rapid MS/MS-bioinformatics-based dereplication to efficiently prioritize new antifungal scaffolds. Screening and revealed novel lipopeptaibiotics, coniotins, from WAC11161, which were undetectable in crude extracts.
View Article and Find Full Text PDFChemistry
January 2025
Kobe University, Department of Chemical Science & Engineering, 1-1 Rokkodaicho, Nada-ku, 657-8501, Kobe, JAPAN.
Organelle targeting is a useful approach in drug development for cancer therapy. Peptide amphiphiles are good candidates for targeting specific organelles because they can be engineered into a wide range of molecular structures, enabling customization for specific functional needs. We have developed a peptide amphiphile, C16-(EY)3, that can respond to tyrosine kinase activity and undergo phosphorylation inside cancer cells.
View Article and Find Full Text PDFSci Rep
January 2025
Biological Engineering Program, Faculty of Engineering, King Mongkut's University of Technology Thonburi, Bangkok, 10140, Thailand.
Nanobodies (Nbs) hold great potential to replace conventional antibodies in various biomedical applications. However, conventional methods for their discovery can be time-consuming and expensive. We have developed a reliable protein selection strategy that combines magnetic activated cell sorting (MACS)-based screening of yeast surface display (YSD) libraries and functional ligand-binding identification by Tat-based recognition of associating proteins (FLI-TRAP) to isolate antigen-specific Nbs from synthetic libraries.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, People's Republic of China. Electronic address:
Telomere repeat-binding factor 2 (TRF2) is a crucial component of the shelterin complex, commonly overexpressed in osteosarcoma (OS) and positively correlated with its progression. To date, effective TRF2 inhibitors for in vivo applications remain limited. In this study, a series of Flavokavain B derivatives were designed and synthesized, and their TRF2 inhibition and antitumor activity were evaluated.
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