HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Asparagine synthetase chemotherapy.

Abstract
Modern clinical treatments of childhood acute lymphoblastic leukemia (ALL) employ enzyme-based methods for depletion of blood asparagine in combination with standard chemotherapeutic agents. Significant side effects can arise in these protocols and, in many cases, patients develop drug-resistant forms of the disease that may be correlated with up-regulation of the enzyme glutamine-dependent asparagine synthetase (ASNS). Though the precise molecular mechanisms that result in the appearance of drug resistance are the subject of active study, potent ASNS inhibitors may have clinical utility in treating asparaginase-resistant forms of childhood ALL. This review provides an overview of recent developments in our understanding of (a) the structure and catalytic mechanism of ASNS, and (b) the role that ASNS may play in the onset of drug-resistant childhood ALL. In addition, the first successful, mechanism-based efforts to prepare and characterize nanomolar ASNS inhibitors are discussed, together with the implications of these studies for future efforts to develop useful drugs.
AuthorsNigel G J Richards, Michael S Kilberg
JournalAnnual review of biochemistry (Annu Rev Biochem) Vol. 75 Pg. 629-54 ( 2006) ISSN: 0066-4154 [Print] United States
PMID16756505 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Sulfonamides
  • Asparagine
  • Aspartate-Ammonia Ligase
Topics
  • Antineoplastic Agents (metabolism, therapeutic use)
  • Asparagine (biosynthesis)
  • Aspartate-Ammonia Ligase (antagonists & inhibitors, chemistry, genetics, metabolism)
  • Binding Sites
  • Cell Cycle (physiology)
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors (metabolism, therapeutic use)
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, enzymology)
  • Protein Conformation
  • Sulfonamides (chemistry)
  • Transcription, Genetic
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: