Table 2.

Properties of selected inhibitors of the proteasome and immunoproteasome

Inhibitor	Development stage	Warhead	Target	Binding kinetics
Bortezomib	Approved for multiple myeloma, relapsed mantle cell lymphoma	Peptide boronic acid analogue165,166	• 20S proteasome: mainly β5 (IC50 values: β5 = 2.4–7.9 nM, β2 = 590–4,200 nM, β1 = 24–74 nM)99,102,103 • Immunoproteasome: β5i, β1i (Refs 73,108,167)	Slowly reversible (Half-life: 110 min)103
Carfilzomib	Phase III (relapsed multiple myeloma)	Peptide epoxyketone99	• 20S proteasome: mainly β5 (IC50 values: β5 = 6 nM, β2 = 3,600 nM, β1 = 2,400 nM)99 • Immunoproteasome: β5i (Refs 73,168)	Irreversible
MLN9708	Phase I	Peptide boronic acid103	• 20S proteasome: mainly β5 (IC50 values: β5 = 3.4 nM, β2 = 3,500 nM, β1 = 31 nM)103 • Immunoproteasome: not reported	Rapidly reversible (Half-life: 18 min)103
CEP18770	Phase I	P2 threonine boronic acid104,106	• 20S proteasome: mainly β5 (IC50 values: β5 = 3.8 nM, β2 = >100 nM, β1 = <100 nM)104,106 • Immunoproteasome: not reported	Slowly reversible
NPI-0052	Phase I	Non-peptide bicyclic γ-lactam β-lactone169	• 20S proteasome: mainly β5, β2 (IC50 values: β5 = 3.5 nM, β2 = 28 nM, β1 = 430 nM)102 • Immunoproteasome: not reported	Irreversible
ONX0912 (formerly PR047)101	Preclinical	Peptide epoxyketone100	• 20S proteasome: β5 (IC50 value = 36 nM) • Immunoproteasome: β5i (IC50 value = 82 nM)	Irreversible
PR957	Preclinical	Peptide epoxyketone107	• 20S proteasome: not reported • Immunoproteasome: β5i-specific (20–40-fold more selective than β5 and β1i)107	Irreversible
IPSI-001	Preclinical	Peptidyl aldehyde108	• 20S proteasome: β5 (Ki value = 105 μM), β1 (Ki value = 239 μM) • Immunoproteasome: β5i (Ki value = 1.03 μM), β1i (Ki value = 1.45 μM)108	Not reported