Michaela Serpi
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View article: Synthesis of Triphosphate Nucleoside Prodrugs: γ‐ProTriPs
Synthesis of Triphosphate Nucleoside Prodrugs: γ‐ProTriPs Open
Although monophosphate nucleoside prodrug approaches have been extensively investigated, leading to the development of several key antiviral and anticancer drugs, less attention has been given to the design of triphosphate prodrugs for the…
View article: Microwave-Accelerated Synthesis of Novel Triphosphate Nucleoside Prodrugs: Expanding the Therapeutic Arsenal of Anticancer Agents
Microwave-Accelerated Synthesis of Novel Triphosphate Nucleoside Prodrugs: Expanding the Therapeutic Arsenal of Anticancer Agents Open
In this study, we report for the first time a microwave-accelerated synthesis of purine and pyrimidine nucleoside triphosphate prodrugs, whose γ phosphate is masked with an aryloxy moiety and an amino acid ester (γ-ProTriP). The synthetic …
View article: Supplementary Figure 1 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Supplementary Figure 1 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Figure S1 related to Figure 2: Genome wide haploid genetic screen identifies genes necessary for the activity of 3'-dA and NUC-7738. A) Number of unique gene trap sense insertions and significant gene hits found in the haploid genetic scre…
View article: Table S2 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Table S2 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Table S2 related to Figure 2: Genome wide haploid genetic screen identifies genes necessary for the activity of 3'-dA and NUC-7738
View article: Table S3 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Table S3 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Table S3 related to Figure 2: Genome wide haploid genetic screen identifies genes necessary for the activity of 3'-dA and NUC-7738.
View article: Supplementary Figure 5 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Supplementary Figure 5 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Figure S5 related to figure 5: NUC-7738 down-regulates cell survival pathways and induces apoptosis. A) A) Renal 786-O and UM-RC-2 cells were treated with NUC-7738 for 24 hours and stained for NF-kB p65 and nuclear dsDNA (DAPI). P65 was se…
View article: Figure 5 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Figure 5 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
NUC-7738 and 3′-dA affect the NF-κB pathway. A, Enrichment plots for NF-κB pathway for all 4 conditions. ES, Enrichment score. B, Expression levels of genes found in the leading edge of NF-κB pathway enrichment. Blue indicates downregulati…
View article: Figure 2 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Figure 2 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Genome-wide haploid genetic screen identifies genes necessary for the activity of 3′-dA and NUC-7738. A, Flowchart of insertional mutagenesis haploid screen. B, Venn diagram illustrating the overlap of genes found in 3′-dA and NUC-7738–tre…
View article: Figure 4 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Figure 4 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Transcription profiling of HAP1 cells treated with 3′-dA and NUC-7738. A, Venn diagram summarizing the number of differentially expressed genes (Padj < 0.05 and −2>FC>2) in 3′-dA and NUC-7738–treated samples. B, Expression heatmap of 91 ge…
View article: Figure 1 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Figure 1 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
NUC-7738, ProTide version 3′-dA, has cytotoxic activity. A, Scheme of the chemical synthesis of 3′-deoxyadenosine 5′-O-phenyl-(benzyloxy-L-alaninyl)-phosphate (NUC-7738), a functionalized ProTide of 3′-dA. B, HAP1 cells were treated with d…
View article: Supplementary Figure 3 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Supplementary Figure 3 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Figure S3 related to figure 4: HINT1 expression across selected cancer types. A) Examples histochemical staining of HINT1 in various types of cancer cells. B) Quantification of HINT1 expression in various types of cancer. The proportion of…
View article: Supplementary Materials from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Supplementary Materials from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
NMR spectra for synthesised compounds
View article: Histological Evaluation of the Effects of Intra-Articular Injection of Caffeic Acid on Cartilage Repair in a Rat Knee Microfracture Model
Histological Evaluation of the Effects of Intra-Articular Injection of Caffeic Acid on Cartilage Repair in a Rat Knee Microfracture Model Open
BACKGROUND Cartilage injuries are challenging to treat due to limited self-healing. Standard treatments often lead to the formation of less durable fibrocartilage. Caffeic acid phenethyl ester (CAPE), a polyphenolic compound, can improve c…
View article: Supplementary Figure 6 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Supplementary Figure 6 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Figure S6 related to figure 6: Transcriptomic profiling of post-treatment biopsy taken from one patient with melanoma. A) Violine plots of expression of genes pre- and post-treatment for all genes which showed, in at least one condition, m…
View article: Supplementary Figure 2 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Supplementary Figure 2 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Figure S2 related to figure 3: Validation of top hits from genome wide haploid screen A) Genes of interest were deleted using an all-in-one gRNA-CRISPR/Cas9 construct and following Puromycin selection. Dose response curves of polyclonal HA…
View article: Data from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Data from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Purpose:Nucleoside analogues form the backbone of many therapeutic regimens in oncology and require the presence of intracellular enzymes for their activation. A ProTide is comprised of a nucleoside fused to a protective phosphoramidate ca…
View article: Figure 3 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Figure 3 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Validation of top hits from genome-wide haploid screen. A, HINT1 was deleted in HAP1 cells using CRISPR/Cas9 technology, as shown by Western blot analysis of HINT1 KO cells using specific antibodies to HINT1. WT and KO cells were treated w…
View article: Supplementary Figure 4 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Supplementary Figure 4 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Figure S4 related to figure 4: Transcriptional profiling of 3'-dA and NUC-7738 treated HAP1 cells. Principal component analysis from RNA sequencing to compare gene expression variance between NUC-7738 and 3'-dA treated cells versus control…
View article: Supplementary Figure 2E from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Supplementary Figure 2E from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Figure S2E related to figure 3: Validation of top hits from genome wide haploid screen. E) mRNA expression levels are given as z-score calculated across all NCI-60 cell lines. mRNA expression levels were obtained from CellMinerTM v2.4.2.
View article: Figure 6 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Figure 6 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Clinical validation of the activity of NUC-7738. A, Intracellular levels of 3′-dATP, 3′-dAMP, and NUC-7738 were measured in the PBMCs from 7 patients who received treatment with NUC-7738 at a dose of 400–900 mg/m2 in the ongoing NuTide:701…
View article: Table S1 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
Table S1 from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Table S1 related to Figure 1: NUC-7738 has cytotoxic activity
View article: Fingolimod phosphoramidate prodrugs: Synthesis, photophysical characterisation and lipid bilayer interaction of fluorescent tagged Prodrug
Fingolimod phosphoramidate prodrugs: Synthesis, photophysical characterisation and lipid bilayer interaction of fluorescent tagged Prodrug Open
FTY720 (Fingolimod, Gilenya, 1), a structural analog of sphingosine (2) was the first orally administered drug approved for the treatment of multiple sclerosis (MS). However, the phosphate derivative of Fingolimod, namely Fingolimod-1-phos…
View article: Design, synthesis and biological evaluation of aryloxy thiophosphoramidate triesters of anticancer nucleoside analogues
Design, synthesis and biological evaluation of aryloxy thiophosphoramidate triesters of anticancer nucleoside analogues Open
Aryloxy phosphoroamidate triesters, known as ProTides, are a class of prodrugs developed to enhance the physicochemical and pharmacological properties of therapeutic nucleosides. This approach has been extensively investigated in the antiv…
View article: Improved Antibacterial Activity of 1,3,4-Oxadiazole-Based Compounds That Restrict <i>Staphylococcus aureus</i> Growth Independent of LtaS Function
Improved Antibacterial Activity of 1,3,4-Oxadiazole-Based Compounds That Restrict <i>Staphylococcus aureus</i> Growth Independent of LtaS Function Open
The lipoteichoic acid (LTA) biosynthesis pathway has emerged as a promising antimicrobial therapeutic target. Previous studies identified the 1,3,4 oxadiazole compound 1771 as an LTA inhibitor with activity against Gram-positive pathogens.…
View article: Synthesis, molecular docking and antibacterial activity of an oxadiazole-based lipoteichoic acid inhibitor and its metabolites
Synthesis, molecular docking and antibacterial activity of an oxadiazole-based lipoteichoic acid inhibitor and its metabolites Open
Amongst drug resistant Gram-positive bacteria, Staphylococcus aureus is a pathogen of great concern as it is the leading cause of life-threatening nosocomial and community acquired infections which are often associated with implanted medic…
View article: Synthesis and Characterization of NUC-7738, an Aryloxy Phosphoramidate of 3′-Deoxyadenosine, as a Potential Anticancer Agent
Synthesis and Characterization of NUC-7738, an Aryloxy Phosphoramidate of 3′-Deoxyadenosine, as a Potential Anticancer Agent Open
3'-Deoxyadenosine (3'-dA, Cordycepin, 1) is a nucleoside analogue with anticancer properties, but its clinical development has been hampered due to its deactivation by adenosine deaminase (ADA) and poor cellular uptake due to low expressio…
View article: The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial
The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms <i>In Vitro</i> and in a First-In-Human Phase I Clinical Trial Open
Purpose: Nucleoside analogues form the backbone of many therapeutic regimens in oncology and require the presence of intracellular enzymes for their activation. A ProTide is comprised of a nucleoside fused to a protective phosphoramidate c…
View article: CCDC 2049153: Experimental Crystal Structure Determination
CCDC 2049153: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …