Related Experiment Video
Updated: Jun 27, 2025
15:22
Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
Published on: April 3, 2014
17.1K
Perspectives and challenges in developing small molecules targeting purine nucleoside phosphorylase
Yangyang Chen1, Yang Li1, Jing Gao1
1Department of Neurology, Laboratory of Neuro-system and Multimorbidity and State Key Laboratory of Biotherapy and Cancer Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
European Journal of Medicinal Chemistry
|May 3, 2024
Summary
Purine nucleoside phosphorylase (PNP) is crucial for cellular functions and immune responses. Inhibitors targeting PNP show promise for treating T-cell cancers and immunological diseases.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Purine nucleoside phosphorylase (PNP) is a cytosolic enzyme central to purine metabolism.
- PNP is implicated in cellular functions, immune responses, and the development of cancers like lymphoma and leukemia.
- Its T-cell targeting profile makes PNP a significant therapeutic target for specific cancers and immunological disorders.
Purpose of the Study:
- To review recent advancements in the development of small-molecule PNP inhibitors.
- To discuss the structure, biological functions, and disease relevance of PNP.
- To explore prospective strategies for designing novel PNP therapeutic agents.
Main Methods:
- Literature review of small-molecule PNP inhibitors.
- Analysis of PNP structure-activity relationships.
- Evaluation of clinical trial data for existing PNP inhibitors.
Main Results:
- Several small-molecule PNP inhibitors have been developed, with Peldesine, Forodesine, and Ulodesine entering clinical trials.
- These inhibitors show potential in treating T-cell leukemia and gout.
- Ongoing research focuses on enhancing inhibitor potency, selectivity, and pharmacokinetic properties.
Conclusions:
- PNP inhibitors represent a promising therapeutic strategy for T-cell malignancies and certain immunological diseases.
- Continued research into PNP inhibitor design is essential for developing more effective treatments.
- Optimizing potency, selectivity, and pharmacokinetics are key future directions for PNP-targeted therapies.
Related Concept Videos
02:54Protein Kinases and Phosphatases
13.1K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.1K
01:26Targets for Drug Action: Overview
6.2K
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...
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...
6.2K
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.4K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.4K
01:19Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K