Table 1.

Principal chemical and pharmacological characteristics of 20S proteasome inhibitors in the treatment of multiple myeloma.

Proteasome inhibitor	Chemical class	Binding kinetics	Route of administration	Half-life (min)	Main therapeutic targets	IC50 β5 (nM)	Maximal proteasome inhibition at MTD (%)
Bortezomib	Boronate	Reversible	IV or SC	110	β5 > β1 > β2	7.9 ± 0.5	65–75
Carfilzomib	Epoxyketone	Irreversible	IV	<30	β5 > β2/β1	<5	>80
Ixazomib	Boronate	Reversible	Oral	18	β5 > β1	3.4	73–99
Oprozomib	Epoxyketone	Irreversible	Oral	30–90	β5	36/82	>80
Marizomib	β-Lactone	Irreversible	IV or oral	10–15	β5 > β2 > β1	3.5 ± 0.3	100

MTD: maximum tolerated dose; IV: intravenous; SC: subcutaneous; IC50: half maximal inhibitory concentration; adapted from Kubiczkova et al.,²⁴ Manasanch et al.⁷ and Boccadoro et al.⁵⁶