Oprozomib (ONX 0912)

Oprozomib (ONX 0912; PR047) is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM.IC50 value: 36 nM/82 nM(20S proteasome β5/LMP7) [1]Target: 20S proteasomeThe anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP, as well as inhibition of migration of MM cells and angiogenesis. Oprozomib is demonstrated an absolute bioavailability of up to 39% in rodents and dogs. It is well tolerated with repeated oral administration at doses resulting in >80% proteasome inhibition in most tissues and elicited an antitumor response in multiple human tumor xenograft and mouse syngeneic models.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Metabolic Enzyme/Protease >> Proteasome

Research Areas >> Cancer

[1]. Zhou HJ, 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.

[2]. Chauhan D, et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood, 2010, 116(23), 4906-4915.

[3]. Muchamuel T, et al. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med, 2009, 15(7), 781-787.

MG-132 | Celastrol | ONX-0914 (PR-957) | Pepstatin | Epoxomicin | Ixazomib (MLN2238) | Calpain Inhibitor I | PD150606 | CEP-18770 (Delanzomib) | RA190 | Capzimin | Gabexate mesylate | PI 1840 | VR23 | PD 151746