An overview of ProTide technology and its implications to drug discovery

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

(2020) Manli Wang et al.   CELL RESEARCH

Radiosynthesis of [18F]-Labelled Pro-Nucleotides (ProTides)

(2020) Alessandra Cavaliere et al.   MOLECULES

Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection

(2020) Emmie de Wit et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Evaluation of NUC-1031: a first-in-class ProTide in biliary tract cancer

(2020) Mansi Arora et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Aryloxy Triester Phosphoramidates as Phosphoserine Prodrugs: A Proof of Concept Study

(2020) Ageo Miccoli et al.   ChemMedChem

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

(2020) Yeming Wang et al.   LANCET

Remdesivir for 5 or 10 Days in Patients with Severe Covid-19

(2020) Jason D. Goldman et al.   NEW ENGLAND JOURNAL OF MEDICINE

NUC-1031/cisplatin versus gemcitabine/cisplatin in untreated locally advanced/metastatic biliary tract cancer (NuTide:121)

(2020) Mairéad Geraldine McNamara et al.   Future Oncology

A Phosphoramidate Strategy Enables Membrane Permeability of a Non-nucleotide Inhibitor of the Prolyl Isomerase Pin1

(2020) Daniel M. C. Schwarz et al.   ACS Medicinal Chemistry Letters

Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice

(2020) Andrea J. Pruijssers et al.   Cell Reports

The nucleotide prodrug CERC ‐913 improves mtDNA content in primary hepatocytes from DGUOK‐deficient rats

(2020) Mark A. Vanden Avond et al.   JOURNAL OF INHERITED METABOLIC DISEASE

Synthesis and biological evaluation of aryl phosphoramidate prodrugs of fosfoxacin and its derivatives

(2019) Mathilde Munier et al.   BIOORGANIC CHEMISTRY

Nucleoside Analogues as Antibacterial Agents

(2019) Jessica M. Thomson et al.   Frontiers in Microbiology

Targeting GNE Myopathy: A Dual Prodrug Approach for the Delivery of N-Acetylmannosamine 6-Phosphate

(2019) Chiara Morozzi et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics

(2019) Sabue Mulangu et al.   NEW ENGLAND JOURNAL OF MEDICINE

Synthesis and biological evaluation of 6-substituted-5-fluorouridine ProTides

(2018) Magdalena Slusarczyk et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Highly convergent synthesis and antiviral activity of (E) -but-2-enyl nucleoside phosphonoamidates

(2018) Maxime Bessières et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses

(2018) Martin S. Davey et al.   JOURNAL OF MEDICINAL CHEMISTRY

The expanding role of prodrugs in contemporary drug design and development

(2018) Jarkko Rautio et al.   NATURE REVIEWS DRUG DISCOVERY

Anti-tumour activity of a first-in-class agent NUC-1031 in patients with advanced cancer: results of a phase I study

(2018) Sarah P. Blagden et al.   BRITISH JOURNAL OF CANCER

Phosphonamidate Prodrugs of a Butyrophilin Ligand Display Plasma Stability and Potent Vγ9 Vδ2 T Cell Stimulation

(2018) Nicholas A. Lentini et al.   JOURNAL OF MEDICINAL CHEMISTRY

The ProTide Prodrug Technology: Where Next?

(2018) Ashwag S. Alanazi et al.   ACS Medicinal Chemistry Letters

Repurposing of nucleoside- and nucleobase-derivative drugs as antibiotics and biofilm inhibitors

(2017) A. E. J. Yssel et al.   JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

The ProTide Prodrug Technology: From the Concept to the Clinic

(2017) Youcef Mehellou et al.   JOURNAL OF MEDICINAL CHEMISTRY

Virtual Screening of Acyclovir Derivatives as Potential Antiviral Agents: Design, Synthesis, and Biological Evaluation of New Acyclic Nucleoside ProTides

(2017) Marco Derudas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization

(2017) Laura Osgerby et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses

(2017) Dustin Siegel et al.   JOURNAL OF MEDICINAL CHEMISTRY

Mechanism-Based Solution to the ProTide Synthesis Problem: Selective Access to Sofosbuvir, Acelarin, and INX-08189

(2017) Bryon Simmons et al.   ORGANIC LETTERS

A multifunctional catalyst that stereoselectively assembles prodrugs

(2017) Daniel A. DiRocco et al.   SCIENCE

Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses

(2017) Timothy P. Sheahan et al.   Science Translational Medicine

Synthetic Approaches for the Preparation of Phosphoramidate Prodrugs of 2′-Deoxypseudoisocytidine

(2017) Michaela Serpi et al.   ChemistryOpen

l-Aspartic and l-glutamic acid ester-based ProTides of anticancer nucleosides: Synthesis and antitumoral evaluation

(2016) Ling-Jie Gao et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

ProTides of BVdU as potential anticancer agents upon efficient intracellular delivery of their activated metabolites

(2016) Sahar Kandil et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Nucleoside Derived Antibiotics to Fight Microbial Drug Resistance: New Utilities for an Established Class of Drugs?

(2016) Michaela Serpi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Diastereoselective synthesis of P-chirogenic phosphoramidate prodrugs of nucleoside analogues (ProTides) via copper catalysed reaction

(2015) F. Pertusati et al.   CHEMICAL COMMUNICATIONS

Nucleoside analogs and tuberculosis: new weapons against an old enemy

(2015) Valentina Ferrari et al.   Future Medicinal Chemistry

ProTides of N-(3-(5-(2′-deoxyuridine))prop-2-ynyl)octanamide as potential anti-tubercular and anti-viral agents

(2014) Christopher McGuigan et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Synthesis of Nucleoside Phosphate and Phosphonate Prodrugs

(2014) Ugo Pradere et al.   CHEMICAL REVIEWS

PMPA and PMEA prodrugs for the treatment of HIV infections and human papillomavirus (HPV) associated neoplasia and cancer

(2014) Fabrizio Pertusati et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Application of ProTide Technology to Gemcitabine: A Successful Approach to Overcome the Key Cancer Resistance Mechanisms Leads to a New Agent (NUC-1031) in Clinical Development

(2014) Magdalena Slusarczyk et al.   JOURNAL OF MEDICINAL CHEMISTRY

Synthesis of an Apionucleoside Family and Discovery of a Prodrug with Anti-HIV Activity

(2014) Kiran S. Toti et al.   JOURNAL OF ORGANIC CHEMISTRY

Chutes and ladders in hepatitis C nucleoside drug development

(2013) Steven J. Coats et al.   ANTIVIRAL RESEARCH

Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate

(2013) Nadege Hamon et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Synthesis and Biological Evaluation of Purine 2′-Fluoro-2′-deoxyriboside ProTides as Anti-influenza Virus Agents

(2013) Silvia Meneghesso et al.   ChemMedChem

Discovery of the First C-Nucleoside HCV Polymerase Inhibitor (GS-6620) with Demonstrated Antiviral Response in HCV Infected Patients

(2013) Aesop Cho et al.   JOURNAL OF MEDICINAL CHEMISTRY

Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases

(2013) Lars Petter Jordheim et al.   NATURE REVIEWS DRUG DISCOVERY

Sofosbuvir for Hepatitis C Genotype 2 or 3 in Patients without Treatment Options

(2013) Ira M. Jacobson et al.   NEW ENGLAND JOURNAL OF MEDICINE

Design, synthesis, and biological evaluation of C1–phosphonamidate analogues of 2-deoxy-d-ribose-1-phosphate

(2013) Maurizio Quintiliani et al.   TETRAHEDRON

Synthesis and biological evaluation of pyrimidine nucleoside monophosphate prodrugs targeted against influenza virus

(2012) Silvia Meneghesso et al.   ANTIVIRAL RESEARCH

1188 GS-6620, A LIVER-TARGETED NUCLEOTIDE PRODRUG, EXHIBITS ANTIVIRAL ACTIVITY AND FAVORABLE SAFETY PROFILE OVER 5 DAYS IN TREATMENT NAIVE CHRONIC HCV GENOTYPE 1 SUBJECTS

(2012) E. Lawitz et al.   JOURNAL OF HEPATOLOGY

Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-naïve patients with HCV genotype 1: A randomized, 28-day, dose-ranging trial

(2012) Maribel Rodriguez-Torres et al.   JOURNAL OF HEPATOLOGY

Novel Phosphoramidate Prodrugs of N-Acetyl-(d)-Glucosamine with Antidegenerative Activity on Bovine and Human Cartilage Explants

(2012) Michaela Serpi et al.   JOURNAL OF MEDICINAL CHEMISTRY

INX-08189, a Phosphoramidate Prodrug of 6-O-Methyl-2′-C-Methyl Guanosine, Is a Potent Inhibitor of Hepatitis C Virus Replication with Excellent Pharmacokinetic and Pharmacodynamic Properties

(2011) John H. Vernachio et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

The clinical potential of the acyclic (and cyclic) nucleoside phosphonates. The magic of the phosphonate bond

(2011) Erik De Clercq   BIOCHEMICAL PHARMACOLOGY

Phosphoramidate ProTides of the Anticancer Agent FUDR Successfully Deliver the Preformed Bioactive Monophosphate in Cells and Confer Advantage over the Parent Nucleoside

(2011) Christopher McGuigan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Synthesis of Diastereomerically Pure Nucleotide Phosphoramidates

(2011) Bruce S. Ross et al.   JOURNAL OF ORGANIC CHEMISTRY

Application of the phosphoramidate ProTide approach to the antiviral drug ribavirin

(2010) Marco Derudas et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Design, synthesis and evaluation of a novel double pro-drug: INX-08189. A new clinical candidate for hepatitis C virus

(2010) Christopher McGuigan et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Mechanism of Activation of PSI-7851 and Its Diastereoisomer PSI-7977

(2010) Eisuke Murakami et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A New Class of Dual‐Targeted Antivirals: Monophosphorylated Acyclovir Prodrug Derivatives Suppress Both Human Immunodeficiency Virus Type 1 and Herpes Simplex Virus Type 2

(2010) Christophe Vanpouille et al.   JOURNAL OF INFECTIOUS DISEASES

Diastereoselective Synthesis of Aryloxy Phosphoramidate Prodrugs of 3′-Deoxy-2′,3′-didehydrothymidine Monophosphate

(2010) Cristina Arbelo Roman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Phosphoramidate ProTides of 2′-C-Methylguanosine as Highly Potent Inhibitors of Hepatitis C Virus. Study of Their in Vitro and in Vivo Properties

(2010) Christopher McGuigan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a β-d-2′-Deoxy-2′-α-fluoro-2′-β-C-methyluridine Nucleotide Prodrug (PSI-7977) for the Treatment of Hepatitis C Virus

(2010) Michael J. Sofia et al.   JOURNAL OF MEDICINAL CHEMISTRY

The application of the phosphoramidate ProTide approach confers micromolar potency against Hepatitis C virus on inactive agent 4′-azidoinosine: Kinase bypass on a dual base/sugar modified nucleoside

(2009) Christopher McGuigan et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The application of phosphoramidate ProTide technology to the potent anti-HCV compound 4′-azidocytidine (R1479)

(2009) Christopher McGuigan et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Prodrug approaches to improving the oral absorption of antiviral nucleotide analogues

(2009) Larryn W Peterson et al.   Expert Opinion on Drug Delivery

The Application of Phosphoramidate Protide Technology to Acyclovir Confers Anti-HIV Inhibition

(2009) Marco Derudas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Successful kinase bypass with new acyclovir phosphoramidate prodrugs

(2008) Christopher McGuigan et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Phosphate Prodrugs Derived fromN-Acetylglucosamine Have Enhanced Chondroprotective Activity in Explant Cultures and Represent a New Lead in Antiosteoarthritis Drug Discovery

(2008) Christopher McGuigan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Activation ofp16Gene Silenced by DNA Methylation in Cancer Cells by Phosphoramidate Derivatives of 2′-Deoxyzebularine

(2008) Christine B. Yoo et al.   JOURNAL OF MEDICINAL CHEMISTRY