title: Spotlight on ixazomib: potential in the treatment of multiple myeloma.
abstract: Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs) such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical properties, mechanisms of action, preclinical efficacy, and clinical trial results leading to the US Food and Drug Administration approval of ixazomib.
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University in St Louis School of Medicine, St Louis, MO, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Muz
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University in St Louis School of Medicine, St Louis, MO, USA; Department of Pharmaceutical and Administrative Sciences, St Louis College of Pharmacy, St Louis, MO, USA.
authors.forename: Rachel Nicole
authors.initials: RN
authors.lastname: Ghazarian
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University in St Louis School of Medicine, St Louis, MO, USA; Department of Biology, St Louis University, St Louis, MO, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Ou
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University in St Louis School of Medicine, St Louis, MO, USA.
authors.forename: Micah John
authors.initials: MJ
authors.lastname: Luderer
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University in St Louis School of Medicine, St Louis, MO, USA; Department of Pharmaceutical and Administrative Sciences, St Louis College of Pharmacy, St Louis, MO, USA.
authors.forename: Hubert Daniel
authors.initials: HD
authors.lastname: Kusdono
authors.affiliation: Department of Radiation Oncology, Cancer Biology Division, Washington University in St Louis School of Medicine, St Louis, MO, USA.
authors.forename: Abdel Kareem
authors.initials: AK
authors.lastname: Azab
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001896:Boron Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D017277:Drug Approval; D019008:Drug Resistance, Neoplasm; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D061988:Proteasome Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D001896:Boron Compounds; D061988:Proteasome Inhibitors; C548400:ixazomib; D005998:Glycine
keywords: biological mechanism; clinical trials; oral administration; proteasome inhibitor
references.citation: Expert Opin Emerg Drugs. 2012 Sep;17(3):407-38
references.pmid: 22920042
references.citation: Asian Pac J Cancer Prev. 2015;16(5):2093-8
references.pmid: 25773856
references.citation: Haematologica. 2014 Mar;99(3):e33-4
references.pmid: 24532044
references.citation: Bioorg Med Chem Lett. 1998 Feb 17;8(4):333-8
references.pmid: 9871680
references.citation: Blood. 2014 Aug 14;124(7):1038-46
references.pmid: 24920586
references.citation: Leuk Res Treatment. 2014;2014:976567
references.pmid: 24829804
references.citation: Curr Pharm Des. 2013;19(22):4025-38
references.pmid: 23181572
references.citation: Blood. 2012 Feb 9;119(6):1468-78
references.pmid: 22096244
references.citation: Lancet Oncol. 2011 May;12(5):431-40
references.pmid: 21507715
references.citation: Mol Pharm. 2012 Aug 6;9(8):2197-205
references.pmid: 22734651
references.citation: Curr Hematol Malig Rep. 2015 Dec;10(4):395-404
references.pmid: 26338470
references.citation: Blood. 2012 Jun 14;119(24):5782-94
references.pmid: 22394600
references.citation: Ann N Y Acad Sci. 2015 Jan;1335:45-62
references.pmid: 25424768
references.citation: Cancer Res. 2010 Mar 1;70(5):1970-80
references.pmid: 20160034
references.citation: Clin Cancer Res. 2011 Aug 15;17(16):5311-21
references.pmid: 21724551
references.citation: Haematologica. 2012 Dec;97(12):1925-8
references.pmid: 22689676
references.citation: Haematologica. 2015 May;100(5):e207-10
references.pmid: 25596270
references.citation: Drugs Today (Barc). 2013 Sep;49(9):563-73
references.pmid: 24086952
references.citation: Blood Cancer J. 2015;5:e338
references.pmid: 26275080
references.citation: J Oncol Pharm Pract. 2013 Dec;19(4):348-54
references.pmid: 23292972
references.citation: Blood. 2007 Nov 1;110(9):3281-90
references.pmid: 17591945
references.citation: Blood. 2012 Nov 8;120(19):3958-67
references.pmid: 22983447
references.citation: Clin Cancer Res. 2014 Mar 15;20(6):1542-54
references.pmid: 24486586
references.citation: Blood. 2012 Jul 5;120(1):20-30
references.pmid: 22535658
references.citation: Leukemia. 2009 Mar;23(3):435-41
references.pmid: 19039321
references.citation: Blood. 2009 Jul 16;114(3):619-29
references.pmid: 19443661
references.citation: Curr Cancer Drug Targets. 2014;14(6):517-36
references.pmid: 25092212
references.citation: Leuk Lymphoma. 2015 Jan;56(1):26-33
references.pmid: 24678978
references.citation: Chem Soc Rev. 2011 Jul;40(7):3895-914
references.pmid: 21431144
references.citation: Blood. 2014 Sep 18;124(12):1905-14
references.pmid: 25079359
references.citation: Biochem Biophys Res Commun. 2007 Sep 21;361(2):549-54
references.pmid: 17662692
references.citation: Blood. 2009 Apr 30;113(18):4341-51
references.pmid: 19139079
references.citation: Lancet Oncol. 2014 Dec;15(13):1503-12
references.pmid: 25456369
references.citation: Onco Targets Ther. 2014 Sep 29;7:1793-800
references.pmid: 25302026
references.citation: Am Soc Clin Oncol Educ Book. 2015;:e504-11
references.pmid: 25993216
references.citation: Clin Adv Hematol Oncol. 2015 Apr;13(4):236-48
references.pmid: 26352582
references.citation: Nat Prod Rep. 2013 May;30(5):600-4
references.pmid: 23575525
references.citation: Immunol Rev. 2015 Jan;263(1):160-72
references.pmid: 25510276