Oprozomib

Oprozomib (PR-047) is an orally bioavailable and selective peptide epoxyketone proteasome inhibitor with IC₅₀s of 36 and 82 nM for proteasome (β5) and immunoproteasome (LMP7), respectively. Oprozomib (ONX 0912) induces apoptosis in MM cells^[1]. In Vitro: Oprozomib inhibits 20S chymotrypsin-like (CT-L) with an IC₅₀ of 55?±?19?nM. Oprozomib inhibits human leukemia Molt-4 cells CT-L with an IC₅₀ of 66 nM^[1].
Oprozomib (ONX 0912; 1-1000 nM; 48 hours) significantly decreases the viability of human multiple myeloma (MM) cell lines^[2].
The anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP^[2]. In Vivo: Oprozomib (PR-047) selectively inhibits chymotrypsin-like (CT-L) activity of both the constitutive proteasome (β5) and immunoproteasome (LMP7) and demonstrates an absolute bioavailability of up to 39% in rodents and dogs^[1].
Oprozomib promotes antitumor activity in multiple animal models by oral administration at doses below the maximum tolerated dose (MTD)^[1].
Oprozomib (30?mg/kg by oral gavage once daily for 5 consecutive days followed by 2 days of rest) treatment decreases tumor burden in C57Bl/6 and NOD.SCID.IL2Rγ^-/- mice^[3].