Targeting XIAP for the treatment of malignancy.
X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis proteins family of caspase inhibitors that selectively binds and inhibits caspases-3, -7 and -9, but not caspase-8. As such, XIAP blocks a substantial portion of the apoptosis pathway and is an attractive target for novel therapeutic agents for the treatment of malignancy. Antisense oligonucleotides directed against XIAP are effective in vitro and are currently being evaluated in clinical trials. Small molecule XIAP inhibitors that target the baculovirus IAP repeat (BIR) 2 or BIR 3 domain are in preclinical development and are advancing toward the clinic. This review will discuss the progress being made in developing antisense and small-molecule XIAP inhibitors.
Schimmer
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AD
The Ontario Cancer Institute, Toronto, Ontario, Canada. aaron.schimmer@utoronto.ca
Dalili
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S
Batey
R A
RA
Riedl
S J
SJ
D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology / Q000627:therapeutic use; D061945:Caspase Inhibitors; D002990:Clobetasol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D016376:Oligonucleotides, Antisense / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D016227:Benzoquinones; D061945:Caspase Inhibitors; D016376:Oligonucleotides, Antisense; D051636:X-Linked Inhibitor of Apoptosis Protein; C004532:quinone; D002990:Clobetasol; D044767:Ubiquitin-Protein Ligases