Discovery of the First Potent and Selective Inhibitors of Human dCTP Pyrophosphatase 1

Journal of Medicinal Chemistry
Sabin Llona-MinguezThomas Helleday

Abstract

The dCTPase pyrophosphatase 1 (dCTPase) regulates the intracellular nucleotide pool through hydrolytic degradation of canonical and noncanonical nucleotide triphosphates (dNTPs). dCTPase is highly expressed in multiple carcinomas and is associated with cancer cell stemness. Here we report on the development of the first potent and selective dCTPase inhibitors that enhance the cytotoxic effect of cytidine analogues in leukemia cells. Boronate 30 displays a promising in vitro ADME profile, including plasma and mouse microsomal half-lives, aqueous solubility, cell permeability and CYP inhibition, deeming it a suitable compound for in vivo studies.

References

Sep 1, 1966·Clinica Chimica Acta; International Journal of Clinical Chemistry·K Itaya, M Ui
Feb 21, 2002·The Oncologist·Julian Adams
Aug 11, 2004·Analytical Biochemistry·Mei-Chu LoGeorge Ellestad
Apr 13, 2006·Chemical Research in Toxicology·Victoria ValinluckLawrence C Sowers
Feb 6, 2008·Journal of Medicinal Chemistry·Bruce D DorseyJohn P Mallamo
Sep 24, 2008·Journal of Combinatorial Chemistry·Matthias TreuAlexander Stadler
May 2, 2009·Journal of the American Chemical Society·David M KnappMartin D Burke
May 29, 2010·Microbiology and Molecular Biology Reviews : MMBR·Kou-San Ju, Rebecca E Parales
Jun 8, 2011·Mutation Research·Michael R O'DonovanDavid H Phillips
Jun 15, 2011·Analytical Biochemistry·Robert A CopelandMargaret Porter Scott
Jun 15, 2011·Chembiochem : a European Journal of Chemical Biology·Timothy W CorsonCraig M Crews
Oct 3, 2013·European Journal of Histochemistry : EJH·Y ZhangY Wang
Jan 29, 2014·The Biochemical Journal·Cristina E RequenaDolores González-Pacanowska
Jul 22, 2014·Journal of the American Chemical Society·Tohru KambeBenjamin F Cravatt
Nov 8, 2014·PloS One·Tamami MorisakiKosei Hirakawa
Mar 18, 2015·Journal of Medicinal Chemistry·Scott J HeckerMichael N Dudley
Mar 27, 2015·Chemistry : a European Journal·Sabin Llona-MinguezThomas Helleday

❮ Previous
Next ❯

Citations

Feb 2, 2017·Journal of Medicinal Chemistry·Sabin Llona-MinguezThomas Helleday
May 17, 2017·Journal of Medicinal Chemistry·Sabin Llona-MinguezThomas Helleday
Jul 30, 2017·Nature Chemistry·Diego B Diaz, Andrei K Yudin
Sep 12, 2017·Organic & Biomolecular Chemistry·Sabin Llona-MinguezThomas Helleday
Apr 27, 2018·Nature Reviews. Chemistry·Jonathan W LehmannMartin D Burke
Jun 22, 2016·The Biochemical Journal·Cristina E RequenaAntonio E Vidal
Aug 16, 2018·MedChemComm·Sabin Llona-MinguezThomas Helleday
Aug 5, 2019·Cellular and Molecular Life Sciences : CMLS·Blanca Martínez-ArribasDolores González-Pacanowska
Jun 18, 2020·Frontiers in Chemistry·Maurice MichelUlrika Warpman Berglund
Nov 5, 2020·Natural Product Reports·Lu TongJun O Liu
Jan 19, 2020·Journal of Molecular Biology·Emma ScalettiPål Stenmark
Aug 26, 2020·Organic Letters·Aidan M KellyMartin D Burke

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.