A5058920118- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- bioluminescence and chemiluminescence research
- Cancer-related gene regulation
- Estrogen and related hormone effects
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Synthesis and biological activity
- Immune Cell Function and Interaction
- Immune cells in cancer
- interferon and immune responses
- Folate and B Vitamins Research
- Photoreceptor and optogenetics research
- Acute Myeloid Leukemia Research
- Enzyme Catalysis and Immobilization
- Microbial Metabolic Engineering and Bioproduction
- Sulfur Compounds in Biology
- Steroid Chemistry and Biochemistry
- Nicotinic Acetylcholine Receptors Study
- Pharmacogenetics and Drug Metabolism
- Phenothiazines and Benzothiazines Synthesis and Activities
- PARP inhibition in cancer therapy
- Cell Image Analysis Techniques
- Amino Acid Enzymes and Metabolism
- Nutritional Studies and Diet
IFOM
2019-2025
Recordati (Italy)
2025
European Institute of Oncology
2009-2017
University of Milan
2009-2013
United States Nuclear Regulatory Commission
1977
We report the stereoselective synthesis and biological activity of a novel series tranylcypromine (TCPA) derivatives (14a-k, 15, 16), potent inhibitors KDM1A. The new compounds strongly inhibit clonogenic potential acute leukemia cell lines. In particular three molecules (14d, 14e, 14g) showing selectivity versus MAO A remarkably inhibiting colony formation in THP-1 human cells, were assessed mouse for their preliminary pharmacokinetic. 14d 14e further tested vivo murine promyelocytic model,...
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 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 (LSD1) has been shown to be critical in acute myeloid leukemia (AML) pathogenesis and this led the development of LSD1 inhibitors (LSD1i) which are currently tested clinical trials. Nonetheless, preclinical studies reported that AML cells frequently exhibit intrinsic resistance inhibition, molecular basis for phenomenon is largely unknown. We explored potential involvement mammalian target rapamycin (mTOR) mediating leukemic LSD1i. Strikingly, unlike sensitive...
D-luciferin is the natural substrate of all luciferases that catalyze production light in bioluminescent insects.The present review covers synthesis and derivatives or analogues are substrates inhibitors luciferase from American firefly Photinus pyralis, enzyme more frequently used techniques vitro optical imaging.
S-methylcysteine (SMC) is a minor amino acid naturally excreted in human urine, protective agent against oxidative stress and biotransformation product of the fumigant biocide methyl bromide nicotine. A metabolic source SMC catabolism repair catalytic protein MGMT (EC 2.1.1.37), which specifically removes group from modified DNA nucleotide O-6-methyl-guanine to revert normal GC base pairing. To assess value S-methylmercapturic (SMMA) as candidate biomarkers proliferative phenomena, sensitive...
Innate immune responses to coronavirus infections are highly cell specific. Tissue-resident macrophages, which infected by severe acute respiratory syndrome 2 (SARS-CoV-2) in patients but inconsistently vitro, exert critical conflicting effects secreting both antiviral type I interferons (IFNs) and tissue-damaging inflammatory cytokines. Steroids, the only class of host-targeting drugs approved for treatment disease 2019 (COVID-19), indiscriminately suppress responses, possibly impairing...
2-Cyano-6-hydroxybenzothiazole is the key intermediate for synthesis of d-luciferin, natural substrate firefly luciferases. A new 2-cyano-6-hydroxybenzothiazole has been realized starting from reaction 1,4-benzoquinone with l-cysteine ethyl ester, followed by oxidation-cyclization (R)-2-amino-3-(2,5-dihydroxyphenylsulfanyl)propanoate hydrochloride to 2-carbethoxy-6-hydroxybenzothiazole. suitable protection this and a conversion corresponding nitrile gave, after deprotection, (32% yield...
A few 2,6-disubstituted benzothiazoles have been prepared as reference compounds or starting material for the preparation of derivatives containing positron emitting fluorine in aromatic ring.Their affinity Photinus pyralis luciferase has evaluated and values IC 50 (8.8-45.2µM) suggest that they are competitive inhibitors enzyme.
Background: Histone lysine demethylases (KDMs) are well-recognized targets in oncology drug discovery. They function at the post-translation level controlling chromatin conformation and gene transcription. KDM1A is a flavin adenine dinucleotide-dependent amine oxidase, overexpressed several tumor types, including acute myeloid leukemia, neuroblastoma non-small-cell lung cancer. Among many known monoamine oxidase inhibitors screened for inhibition, tranylcypromine emerged as moderately active...
A few 2-substituted-6-hydroxy and 6-methoxybenzothiazoles have been prepared from ethyl 6hydroxybenzothiazole-2-carboxylate, obtained by oxidation of (R)-2-amino-3-(2,5dihydroxyphenylsulfanyl)propanoate hydrochloride, in turn 1,4-benzoquinone.
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Targeting nuclear mechanics is emerging as a promising therapeutic strategy for sensitizing cancer cells to immunotherapy. Inhibition of the mechano-sensory kinase ATR leads mechanical vulnerability cells, causing envelope softness and collapse activation cGAS-STING-mediated innate immune response. Finding novel compounds that interfere with non-canonical role in controlling presents an intriguing opportunity. We carried out multiparametric high-content screen identify small molecules affect...
Abstract Tissue-resident macrophages exert critical but conflicting effects on the progression of coronavirus infections by secreting both anti-viral type I Interferons and tissue-damaging inflammatory cytokines. Steroids, only class host-targeting drugs approved for Covid19, indiscriminately suppress responses, possibly impairing viral clearance, provide limited clinical benefit. Here we set up a mouse in vitro co-culture system that reproduces macrophage response to SARS-CoV2 seen patients...