Synonyms: MLN-2238 | MLN2238 | Ninlaro®
ixazomib is an approved drug (FDA (2015), EMA (2016))
Compound class:
Synthetic organic
Comment: Ixazomib is the first approved oral proteasome inhibitor. Ixazomib reversibly inhibits 20S proteasome activity. Like bortezomib, ixazomib primarily inhibits the chymotrypsin-like (β5) proteolytic site within the 20S proteasome, but its pharmacokinetics, pharmacodynamics, and antitumor activity are superior to those of bortezomib [3].
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
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No information available. |
Summary of Clinical Use |
Ixazomib is being evaluated in several Phase 3 clinical trials for MM [4], and a single Phase 3 trial for relapsed/refractory systemic light chain amyloidosis. Phase 1 and II trials for other hematological cancers and solid tumours [3] such as bladder cancer and renal cell carcinoma (RCC) are ongoing. Both the European EMA and US FDA have formally recognised the relevance of this drug as a potential therapy for treating serious or life-threatening conditions, in particular systemic light-chain amyloidosis (AL amyloidosis), a condition for which there is currently no approved treatment. The EMA have granted ixazomib orphan drug status and the FDA have granted breakthrough therapy designation for AL amyloidosis. Full US FDA marketing approval was granted in November 2015, for ixazomib to be used in combination with lenalidomide and dexamethasone to treat patients with MM who have received at least one prior therapy. |
Mechanism Of Action and Pharmacodynamic Effects |
Ixazomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome. Inhibitors of proteasome activity are antiproliferative and pro-apoptotic in nature. Proteasome inhibition leads to an increase in intracellular pro-apoptotic proteins, which promote cell-cycle arrest and cell-death [1]. Proteasome activity is reviewed in [2]. |
External links |
For extended ADME data see the following: Electronic Medicines Compendium (eMC) Drugs.com European Medicines Agency (EMA) |