Oprozomib  (Synonyms: ONX 0912; PR-047)

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].

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

532.61

Solid

C₂₅H₃₂N₄O₇S

935888-69-0

C[[email protected]]1(OC1)C([[email protected]](CC2=CC=CC=C2)NC([[email protected]@H](NC([[email protected]@H](NC(C3=CN=C(C)S3)=O)COC)=O)COC)=O)=O

Room temperature in continental US; may vary elsewhere.

• [1]. Han-Jie Zhou, et al. Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). J Med Chem. 2009 May 14;52(9):3028-38.  [Content Brief]

  [2]. Dharminder Chauhan,et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood. 2010 Dec 2;116(23):4906-15.  [Content Brief]

  [3]. M A Hurchla, et al.The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects. Leukemia. 2013 Feb;27(2):430-40.  [Content Brief]