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. Author manuscript; available in PMC: 2020 Nov 19.
Published in final edited form as: J Med Chem. 2019 Apr 19;62(9):4444–4455. doi: 10.1021/acs.jmedchem.8b01943

Figure 6.

Figure 6.

(A) Predicted docking models of UK101 and carfilzomib (Cfz) bound to β5 or β1i. The location of UK101’s TBDMS group positioned within putative P1′ pockets is highlighted using a purple-colored circle. β5 (PDB ID: 3UNB) and β1i (PDB ID: 3UNF) from mammalian 20S proteasomes were used as templates. In cartoon presentation, β1i (gray, PDB ID: 3UNF) was superposed to β5 (yellow, PDB ID: 3UNB) and only different amino acid residues are shown in stick model. (B) Comparison of UK101 and 5(UK101-OH) in terms of their potency (IC50 values) against proteasome chymotrypsin-like activity (in RPMI8226 cell lysate), β1i/LMP2 catalytic activity (in 20S purified human immunoproteasome), and against H23, H727, and Cfz-resistant RPMI8226 cells as measured by MTS cell viability assay. Data are reported as the mean ± SD. Docking model of UK101-OH bound to β1i (PDB ID: 3UNF). The P1′-OH of UK101-OH (5) is perfectly positioned to form hydrogen bonds with Ser168 and Ser21.