The druggability of intracellular nucleotide-degrading enzymes

Chiara Rampazzo1, Maria Grazia Tozzi2, Charles Dumontet3,4,5,6,7,8,9

  • 1Department of Biology, University of Padova, 35131, Padua, Italy.

Insights

Intracellular nucleotide-degrading enzymes are emerging as promising cancer drug targets. Recent research highlights enzymes like Rcl, SAMHD1, MTH1, and cN-II as potential alternatives to traditional chemotherapy.

Area of Science:

  • Biochemistry
  • Oncology
  • Pharmacology

Background:

  • Nucleotide metabolism is a key area for anticancer drug development.
  • Antimetabolites and enzyme inhibitors are established therapeutic strategies.
  • Recent advances have identified novel intracellular nucleotide-degrading enzymes.

Purpose of the Study:

  • To review scientific findings on intracellular nucleotide-degrading enzymes as cancer drug targets.
  • To discuss the therapeutic potential of specific enzymes: Rcl, SAMHD1, MTH1, and cN-II.
  • To highlight these enzymes as alternatives to conventional chemotherapy targets.

Main Methods:

  • Literature review of scientific findings over the last 10-15 years.
  • Analysis of research identifying intracellular nucleotide-degrading enzymes.
  • Discussion of therapeutic applications for specific enzymes.

Main Results:

  • Several intracellular nucleotide-degrading enzymes have been identified as viable cancer drug targets.
  • Enzymes such as Rcl, SAMHD1, MTH1, and cN-II show significant therapeutic potential.
  • These enzymes offer new avenues for cancer treatment.

Conclusions:

  • Intracellular nucleotide-degrading enzymes represent a potent class of anticancer targets.
  • These enzymes offer promising alternatives to conventional chemotherapy.
  • Further investigation into Rcl, SAMHD1, MTH1, and cN-II could lead to novel cancer therapies.

Related Concept Videos

Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
46
Biosynthesis of Nucleic Acids01:28

Biosynthesis of Nucleic Acids

Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
1.5K
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
11.3K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
9.2K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
4.3K
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
62