Ixazomib Citrate

Ixazomib Citrate (CAS No.: 1239908-20-3) is a synthetic second-generation small-molecule research compound with oral bioavailability characteristics, a convertible prodrug of ixazomib, and is widely used as a research-grade inhibitor of the 20S proteasome in the eukaryotic ubiquitin-proteasome system for elucidating mechanisms of protein homeostasis and signal transduction; after conversion to its active form under physiologically relevant conditions, it selectively targets the chymotrypsin-like proteolytic activity of the β5 subunit of the 20S proteasome, and at higher exposure levels inhibits the caspase-like activity of β1 and the trypsin-like activity of β2, thereby weakening regulated protein degradation, leading to accumulation of polyubiquitinated substrates and triggering stress-related cascade reactions, commonly observed as growth inhibition and apoptotic phenotypes in sensitive cell systems; in vitro activity is typically characterized by significant inhibition of the primary β5 site at low nanomolar levels, while effects on secondary sites and various cellular pathways or viability readouts may extend from tens of nanomolar to the micromolar range, with reported assays showing an IC50 of approximately 3.4 nM for the β5 site; in biomedical research and drug discovery, this compound is commonly used for mechanistic studies of protein homeostasis and proteasome dependence, pathway phenotype analysis in hematologic and solid tumor-related cell models, dynamic monitoring of stress kinase and apoptotic cascades, and combination screening with compounds of other mechanisms of action for pathway mapping and target validation; in appropriate animal models, it is also used in exploratory pharmacology and disease biology research to correlate exposure, target occupancy, and pharmacodynamic biomarker responses; the specific concentration or dose used in experiments should be optimized according to the research objective, experimental design, and model sensitivity, and is for research use only, not involving any clinical, dietary, or other non-research applications.