A5063108137- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Mycobacterium research and diagnosis
- CAR-T cell therapy research
- Cannabis and Cannabinoid Research
- Natural product bioactivities and synthesis
- Bipolar Disorder and Treatment
- interferon and immune responses
- Autophagy in Disease and Therapy
- Traditional Chinese Medicine Analysis
- Phase Equilibria and Thermodynamics
- Neuroinflammation and Neurodegeneration Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Monoclonal and Polyclonal Antibodies Research
- Phagocytosis and Immune Regulation
- thermodynamics and calorimetric analyses
University of Trento
2021-2024
ETH Zurich
2024
University of Milan
2021-2023
The inhibition of the PD-1/PD-L1 axis by monoclonal antibodies has achieved remarkable success in treating a growing number cancers. However, novel class small organic molecules, with BMS-202 (1) as lead, is emerging direct PD-L1 inhibitors. Herein, we report series 2,4,6-tri- and 2,4-disubstituted 1,3,5-triazines, which were synthesized assayed for their binding NMR homogeneous time-resolved fluorescence. Among them, compound 10 demonstrated to strongly bind protein challenged it co-culture...
Lipopolysaccharide (LPS) exposure to macrophages induces an inflammatory response, which is regulated at the transcriptional and post-transcriptional levels. HuR (ELAVL1) RNA-binding protein that regulates cytokines chemokines transcripts containing AU/U-rich elements (AREs) mediates LPS-induced response. Here, we show small-molecule tanshinone mimics (TMs) inhibiting HuR-RNA interaction counteract LPS stimulus in macrophages. TMs exist solution keto-enolic tautomerism, molecular dynamic...
The disaccharide trehalose is a well-established autophagy inducer, but its therapeutic application severely hampered by low potency and poor pharmacokinetic profile. Thus, we targeted the rational design synthesis of trehalose-based small molecules nano objects to overcome such issues. Among several rationally designed trehalose-centered putative inducers, coupled via suitable spacers with known self-assembly inducer squalene yield two nanolipid-trehalose conjugates. Squalene for...
Today it is widely recognized that the PD-1/PD-L1 axis plays a fundamental role in escaping immune system cancers, so anti-PD-1/PD-L1 antibodies have been evaluated for their antitumor properties more than 1000 clinical trials. As result, some of them entered market revolutionizing treatment landscape specific cancer types. Nonetheless, new era based on development small molecules as anti PD-L1 drugs has begun. There are, however, limitations to advancing these compounds into stages...
The RNA binding protein Human Antigen R (HuR) has been identified as a main regulator of the innate immune response and its inhibition can lead to beneficial anti-inflammatory effects. To this aim, we previously synthesized novel class small molecules named Tanshinone Mimics (TMs) able interfere with HuR-RNA binding, that dampen LPS-induced response. Herein, present series TMs, encompassing thiophene 3/TM9 4/TM10, furan 5/TM11 6/TM12, pyrrole 7b/TM13, pyrazole 8. furan-containing 5(TM11)...
Abstract Lipopolysaccharide exposure to macrophages induces an inflammatory response that is heavily regulated at the transcriptional and post-transcriptional levels. HuR (ELAVL1) RNA binding protein binds regulates maturation half-life of AU/U rich elements (ARE) containing cytokines chemokines transcripts, mediating LPS-induced response. Here we investigated how what extent small molecule tanshinone mimics (TMs) inhibiting HuR-RNA interaction counteract LPS stimulus in macrophages. We show...
Human antigen R (HuR) is an RNA binding protein (RBP) belonging to the ELAV (Embryonic Lethal Abnormal Vision) family, which stabilizes mRNAs and regulates expression of multiple genes. Its altered or localization related pathological features such as cancer inflammation. Dihydrotanshinone I (DHTS I) a naturally occurring, tetracyclic ortho-quinone inhibitor HuR-mRNA interaction. Our earlier efforts led identification synthetic Tanshinone Mimic (TM) 2 with improved affinity for HuR. Here we...