Design, Synthesis and Evaluation of AdSS Bisubstrate Inhibitors
- Resource Type
- Authors
- Nidhi Tibrewal; Gregory I. Elliott
- Source
- ChemMedChem. 15:2269-2272
- Subject
- Purine
01 natural sciences
Biochemistry
chemistry.chemical_compound
Drug Discovery
medicine
Humans
Moiety
Enzyme Inhibitors
General Pharmacology, Toxicology and Pharmaceutics
Pharmacology
Molecular Structure
biology
010405 organic chemistry
Organic Chemistry
Adenylosuccinate synthase
Purine Nucleosides
Adenosine
Small molecule
0104 chemical sciences
010404 medicinal & biomolecular chemistry
Purine-Nucleoside Phosphorylase
chemistry
Drug Design
biology.protein
Nucleic acid
Molecular Medicine
Linker
Nucleoside
medicine.drug
- Language
- ISSN
- 1860-7187
1860-7179
Many cancers lack the expression of methylthioadenosine phosphorylase (MTAP). These cancers require adenylosuccinate synthetase (AdSS) for nucleic acid synthesis. By inhibiting adenylosuccinate synthetase, we potentially have a new therapeutic agent. Bisubstrate inhibitors were synthesized and evaluated against purified AdSS. The best activity was obtained with adenosine bearing a four-carbon linker that connects the N-formyl-N-hydroxy moiety to the 6-position of the purine nucleoside.