The Core Structure of TMC-95A Is a Promising Lead for Reversible Proteasome Inhibition This work was supported by the SFB 469 of the Ludwig-Maximilians-Universität München and the SPP 1045.

Based on information from the X-ray structure of the TMC-95A/proteasome complex, TMC-95A (A) was reduced to the minimum core structure (B). The inhibitory potency of the synthetic analogue confirms that the simplified ring structure may well serve as the lead for further improvement of affinity and selectivity of reversible proteasome inhibitors.