Oprozomib

SKU: orb1223597

Description

Oprozomib (ONX-0912;PR-047) is a potent, orally bioavailable proteasome inhibitor that inhibits chymotrypsin-like (CT-L) activity of 20S proteasome β5/LMP7 with IC50 of 36/82 nM; triggers apoptosis in MM cells, associated with PARP cleavage and caspase activation, causes in vitro and in vivo cytotoxicity in multiple myeloma, also enhances anti-MM activity of bortezomib, lenalidomide dexamethasone, or pan-histone deacetylase inhibitor.Blood Cancer Phase 2 Clinical(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.Oprozomib (ONX 0912; 1-1000 nM; 48 hours) significantly decreases the viability of human multiple myeloma (MM) cell lines.The anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP.(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.Oprozomib promotes antitumor activity in multiple animal models by oral administration at doses below the maximum tolerated dose (MTD).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.

Key Properties

• CAS Number: 935888-69-0
• MW: 532.6092
• Purity: >98% (HPLC)
• Formula: C₂₅H₃₂N₄O₇S
• SMILES: O=C(C1=CN=C(C)S1)N[C@@H](COC)C(N[C@@H](COC)C(N[C@@H](CC2=CC=CC=C2)C([C@]3(C)OC3)=O)=O)=O
• Target: Proteasome
• Solubility: DMSO: ≥ 50 mg/mL

Bioactivity

• 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. Oprozomib promotes antitumor activity in multiple animal models by oral administration at doses below the maximum tolerated dose (MTD). 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. Animal model: C57Bl/6 and NOD. SCID. IL2Rγ-/-mice bearing established human RPMI-8226-luc myeloma cells. Dosage: 30 mg/kg. Administration: Oral gavage once daily for 5 consecutive days followed by 2 days of rest. Result: Decreased human MM tumor burden and protects mice from bone destruction.
• 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. Oprozomib (ONX 0912; 1-1000 nM; 48 hours) significantly decreases the viability of human multiple myeloma (MM) cell lines. The anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP. Cell Viability Assay Cell line: Human MM cell lines (MM.1S, INA-6, RPMI-8226, MM.1R, Dox-40, KMS12, and OPM2) Concentration: 1, 10, 100, 1000 nM. Incubation time: 48 hours. Result: Exhibited anti-MM activity. Western blot analysis. Cell line: MM.1S cells Concentration: 7 nM and 10 nM. Incubation time: 48 hours. Result: Treatment with 3 nM triggered a marked increase in proteolytic cleavage of PARP, a signature event during apoptosis. Induced cleavage of caspase-3, an upstream activator of PARP. Induced activation of both casapse-8 (extrinsic) and caspase-9 (intrinsic) apoptotic pathways.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ONX-0912 | ONX0912 | ONX 0912 | PR-047 | PR047 | PR 047

Quick Database Links

Gene Symbol

Proteasome