A5012247240- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Chemical synthesis and alkaloids
- Cholinesterase and Neurodegenerative Diseases
- Phosphodiesterase function and regulation
- Click Chemistry and Applications
- Plant biochemistry and biosynthesis
- Advanced biosensing and bioanalysis techniques
- Natural product bioactivities and synthesis
- Crystallization and Solubility Studies
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- X-ray Diffraction in Crystallography
- Traditional Chinese Medicine Analysis
IFOM
2022-2025
European Institute of Oncology
2017-2020
University of Genoa
2007-2016
The balance of methylation levels at histone H3 lysine 4 (H3K4) is regulated by KDM1A (LSD1). overexpressed in several tumor types, thus representing an emerging target for the development novel cancer therapeutics. We have previously described ( Part 1, DOI 10.1021.acs.jmedchem.6b01018 ) identification thieno[3,2-b]pyrrole-5-carboxamides as reversible inhibitors KDM1A, whose preliminary exploration resulted compound 2 with biochemical IC50 = 160 nM. now report structure-guided optimization...
Lysine specific demethylase 1 KDM1A (LSD1) regulates histone methylation and it is increasingly recognized as a potential therapeutic target in oncology. We report on high-throughput screening campaign performed KDM1A/CoREST, using time-resolved fluorescence resonance energy transfer (TR-FRET) technology, to identify reversible inhibitors. The led 115 hits for which we determined biochemical IC50, thus identifying four chemical series. After data analysis, have prioritized the series of...
The lack of selective inhibitors toward the long, short, or supershort phosphodiesterases (PDE4s) prevented researchers from carefully defining connection between different enzyme isoforms, their brain localization, and role in neurodegenerative diseases such as Alzheimer's disease (AD). In search for new therapeutic agents treating memory learning disorders, we synthesized rolipram related PDE4 inhibitors, which had some selectivity long form PDE4D3. first series was racemate then resolved...
Lysine-specific demethylase 1 (LSD1 or KDM1A) is a FAD-dependent enzyme that acts as transcription corepressor coactivator by regulating the methylation status of histone H3 lysines K4 and K9, respectively. KDM1A represents an attractive target for cancer therapy. While, in past, main medicinal chemistry strategy toward inhibition was based on optimization ligands irreversibly bind FAD cofactor within catalytic site, we others have also identified reversible inhibitors. Herein reported...
The relative stereochemistry of 3,4-secoisopimara-4(18),7,15-triene-3-oic acid, a diterpenoid with antispasmodic, hypotensive and antibacterial activities isolated from Salvia cinnabarina, was determined by an X-ray diffraction analysis single crystal suitable crystalline derivative.