Class/mechanism: Second-generation reversible proteasome inhibitor; preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome. Ixazomib interferes with degradation of ubiquitinated proteins, which disrupts normal homeostatic mechansims, leading to cell death. The tissue distribution profile of ixazomib may be different than Bortezomib (Velcade) due to a shorter 20S proteasome dissociation half-life. Upon exposure to aqueous solutions, ixazomib/MLN9708 hydrolyzes to MLN2238, the active form.
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Diseases for which it is used
Patient drug information
History of changes in FDA indication
- 2015-11-20: FDA approved in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. (Based on TOURMALINE-MM1)
History of changes in EMA indication
- 2016-11-21: Initial conditional approval
Also known as
- Code names: MLN2238, MLN9708
- Brand name: Ninlaro
- ↑ 1.0 1.1 1.2 Ixazomib (Ninlaro) package insert
- ↑ Ixazomib (Ninlaro) package insert (locally hosted backup)
- ↑ Ninlaro manufacturer's website
- ↑ Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, Yu J, Yang Y, Hales P, Bruzzese F, Liu J, Blank J, Garcia K, Tsu C, Dick L, Fleming P, Yu L, Manfredi M, Rolfe M, Bolen J. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010 Mar 1;70(5):1970-80. Epub 2010 Feb 16. PubMed
- ↑ Siegfried Janz, Brian G Van Ness, Vishala Neppalli, Ray Liu, Michael D Pickard, Jennifer Terkelsen, Daniel Bradley, Ling Hu, Erik Kupperman, Mark Manfredi, and Edmund Lee. The Novel Proteasome Inhibitor MLN9708 Demonstrates Efficacy in a Genetically-Engineered Mouse Model of De Novo Plasma Cell Malignancy. 2009 ASH Annual Meeting oral poster 3849.
- ↑ Aisha Masood, MD, Kasyapa Chitta, PhD, Kiersten M Miles, PhD, Nazmul H Khan, PhD, Remi Adelaiye, Drusilla Akhtar, Taimur Sher, MD, and Asher A. Chanan-Khan, MD. An Investigational Proteasome Inhibitor MLN9708 (MLN2238) Induces Apoptosis In Human Multiple Myeloma Cells In Vitro. 2010 ASH Annual Meeting oral poster 3066.
- ↑ Paul G. Richardson, MD, Rachid Baz, MD, Luhua Wang, MD, Andrzej J Jakubowiak, MD, PhD, Deborah Berg, RN, MSN, Guohui Liu, PhD, Neeraj Gupta, PhD, Alessandra Di Bacco, PhD, Ai-Min Hui, MD, and Sagar Lonial, MD. Investigational Agent MLN9708, An Oral Proteasome Inhibitor, in Patients (Pts) with Relapsed and/or Refractory Multiple Myeloma (MM): Results From the Expansion Cohorts of a Phase 1 Dose-Escalation Study. 2011 ASH Annual Meeting oral poster 301.
- ↑ Takeda to Present Data from Ixazomib's [TOURMALINE MM-1] Phase 3 Study in Relapsed/Refractory Multiple Myeloma at Upcoming  American Society of Hematology Annual Meeting