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.
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| http://dx.doi.org/10.5812/ijpr-129251 | DOI Listing |
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