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PSI is a synthetic peptide proteasome inhibitor.1,2,3 It inhibits the acidic and neutral chymotrypsin-like activities of the 20S proteasome (IC50s = 0.25 and 6.5 μM, respectively).3 PSI is cytotoxic to HL-60, KG-1a, RWLeu-4, AR230, and K562 human leukemia cells (IC50s = 4.9, 17.5, 7.8, 7.3, and 10 nM, respectively).4 It selectively induces apoptosis in subconfluent bovine aortic endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs; EC50s = 24 and 7 nM, respectively) over confluent BAECs and HUVECs (EC50s = 8,150 and 7,830 nM, respectively).5 PSI induces accumulation of ubiquitin-protein conjugates in HT4 mouse neuronal cells.6

1.Collins, G.A., and Goldberg, A.L.The logic of the 26S proteasomeCell169(5)792-806(2017) 2.Orlowski, M., and Wilk, S.Catalytic activities of the 20 S proteasome, a multicatalytic proteinase complexArch. Biochem. Biophys.383(1)1-16(2000) 3.Figueiredo-Pereira, M.E., Chen, W.-E., Yuan, H.-M., et al.A novel chymotrypsin-like component of the multicatalytic proteinase complex optimally active at acidic pHArch. Biochem. Biophys.317(1)69-78(1995) 4.Soligo, D., Servida, F., Delia, D., et al.The apoptogenic response of human myeloid leukaemia cell lines and of normal and malignant haematopoietic progenitor cells to the proteasome inhibitor PSIBr. J. Haematol.113(1)126-135(2001) 5.Drexler, H.C., Risau, W., and Konerding, M.A.Inhibition of proteasome function induces programmed cell death in proliferating endothelial cellsFASEB J.14(1)65-77(2000) 6.Figueiredo-Pereira, M.E., Berg, K.A., and Wilk, S.A new inhibitor of the chymotrypsin-like activity of the multicatalytic proteinase complex (20S proteasome) induces accumulation of ubiquitin-protein conjugates in a neuronal cellJ. Neurochem.63(4)1578-1581(1994)

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