Oprozomib

Summary

Oprozomib (ONX 0912) is an orally bioavailable, next-generation epoxyketone proteasome inhibitor structurally related to carfilzomib. It was developed to provide oral dosing convenience for treatment of hematologic malignancies, particularly multiple myeloma and Waldenström's macroglobulinemia. Clinical development has been conducted through Phase I/II trials.

Mechanism of Action

Irreversibly inhibits the chymotrypsin-like activity of the 20S proteasome by covalently binding to the N-terminal threonine residue of the beta-5 subunit, leading to accumulation of ubiquitinated proteins, induction of apoptosis, and cell cycle arrest in malignant cells.

Routes of Administration

Goals & Uses

• Proteasome inhibitor resistance circumventionOncologyLow
• Multiple myeloma treatmentOncologyModerate
• Non-Hodgkin lymphoma treatmentOncologyLow
• Waldenström's macroglobulinemia treatmentOncologyLow

Contraindications

• Severe hepatic impairmentOrganHighLiver function concerns
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Known hypersensitivity to oprozomib or excipientsAllergyHigh

Adverse Effects

• Peripheral neuropathyNeurologicalUncommon
• ThrombocytopeniaHematologicCommonLow platelet count
• Gastrointestinal toxicity (nausea, vomiting, diarrhea)GastrointestinalCommon
• AnemiaHematologicCommonLow red blood cell count or hemoglobin
• FatigueGeneralCommonLow energy or tiredness
• Cardiac adverse eventsCardiovascularUncommon

Drug Interactions

• Anticoagulants (e.g., warfarin)Moderate
• CYP3A4 inducers (e.g., rifampin, carbamazepine)Moderate
• DexamethasoneLow
• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)Moderate

Population Constraints

• Severe renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative
• Pregnant or breastfeeding womenReproductiveRelative
• Patients with pre-existing cardiac diseaseCardiovascularRelative

Regulatory Status

• European UnionInvestigationalNo EMA marketing authorization; clinical trials conducted in EU sites.
• United StatesInvestigationalFDA Orphan Drug Designation granted for multiple myeloma; no approved indications as of knowledge cutoff.
• United KingdomInvestigationalNo MHRA approval; investigational use only.

Oprozomib has not received FDA, EMA, or other regulatory approval as of the knowledge cutoff. It remains in investigational status with no approved indications. Orphan Drug Designation was granted by the FDA for multiple myeloma.

Evidence & Sources

No sources recorded yet.