A5069161511- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Protein Degradation and Inhibitors
- Cellular transport and secretion
- Calcium signaling and nucleotide metabolism
- Synthesis and Biological Evaluation
- Immunotherapy and Immune Responses
- Cancer, Stress, Anesthesia, and Immune Response
- Computational Drug Discovery Methods
- Tuberculosis Research and Epidemiology
Jagiellonian University
2024
We present new small-molecular probes targeting the human PD-L1 protein. The molecules were designed by incorporating a newly discovered N-methylmorpholine substituent into known biphenyl-based structure. Four prototype derivatives of 4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-carbonitrile (STD4), comprising morpholine fused with biphenyl core at different orientations first verified for their potential binding to using molecular docking method. A more favorable 7-phenyl derivative STD4...
Lysosome-targeting chimeras (LYTACs) have recently been developed to facilitate the lysosomal degradation of specific extracellular and transmembrane molecular targets. However, LYTAC particles described date are based on glycopeptide conjugates, which difficult prepare produce a large scale. Here, we report development pure protein LYTACs non-glycosylated IGF2 peptides, can be readily produced in virtually any facility capable monoclonal antibody production. These utilize IGF2R/CI-M6PR...
Pursuing our recent findings from the fragment-based screening, we now propose new compounds targeting human PD-L1 protein. The comprise several favorable features of molecules published in previous years and contain a newly discovered N‑methylmorpholine substituent incorporated into biphenyl-based structure. Four prototype molecule derivatives 4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-carbonitrile (STD4), comprising morpholine fused with biphenyl core at different orientations were...
Therapeutic antibodies directed against either programmed cell death-1 protein (PD-1) or its ligand PD-L1 have demonstrated efficacy in the treatment of various cancers. In contrast with antibodies, small molecules potential for increased tissue penetration; better pharmacology; and therefore, improved antitumor activity. A series nonsymmetric C2 inhibitors were synthesized evaluated PD-1/PD-L1 interaction inhibition. These compounds induced dimerization effectively blocked PD-L1/PD-1 a...
Abstract Lysosome Targeting Chimeras (LYTACs) have recently been developed to facilitate lysosomal degradation of specific extracellular and transmembrane molecular targets. However, the LYTAC particles described date are based on glycopeptide conjugates, which difficult prepare produce a large scale. Here we report development pure protein LYTACs non-glycosylated IGF2 peptides, can be readily produced in virtually any facility capable monoclonal antibody production. These chimeras utilize...