Synthesis and Biological Evaluation of Novel Anti-leukemia Proteolysis-Targeting Chimeras in Degradating Inosine Monophosphate Dehydrogenase
| Author | Hamidreza Sohbati | en |
| Author | Mohsen Amini | en |
| Author | Saeed Balalaie | en |
| Orcid | Saeed Balalaie [0000-0002-5764-0442] | en |
| Issued Date | 2022-12-31 | en |
| Abstract | Background: Proteolysis-targeting chimera (PROTAC) is a bifunctional molecule comprising a ligand to recognize the targeted protein to be degraded. Objectives: To use the advantages of the PROTAC technique, we have synthesized novel compounds to degrade inosine monophosphate dehydrogenase (IMPDH) by the proteasome system. Methods: We describe the synthesis of new PROTACs based on a combination of mycophenolic acid (MPA) as the potent IMPDH inhibitor and pomalidomide as a ligand of E3 ubiquitin ligase via linkers formed from Cu(I)-catalyzed cycloaddition reaction. Results: All synthesized compounds were investigated against Jurkat cells as acute T-cell leukemia and were potent apoptosis inducers at 50 nM. Conclusion: The effect of compound 2 in 0.05 μM on IMPDH degradation can be almost prevented by competition with bortezomib as the proteasome inhibitor at 0.1 and 0.5 μM. | en |
| DOI | https://doi.org/10.5812/ijpr-129251 | en |
| Keyword | Anti-leukemia | en |
| Keyword | Inosine Monophosphate Dehydrogenase | en |
| Keyword | Mycophenolic Acid | en |
| Keyword | Proteolysis-Targeting Chimeras | en |
| Keyword | Triazole | en |
| Publisher | Brieflands | en |
| Title | Synthesis and Biological Evaluation of Novel Anti-leukemia Proteolysis-Targeting Chimeras in Degradating Inosine Monophosphate Dehydrogenase | en |
| Type | Research Article | en |