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Chemical structures of small molecule 20S PIs tested in this study. The respective P1 residues (Leu in bortezomib; cyclohexenyl in salinosporamides A, B, K, and cinnabaramide A; and the boxed residues in the salinosporamide X series) interact with the S1 specificity pocket of the proteasome β-subunit upon binding. The displaceable chloride of salinosporamide A confers irreversible inhibition.
