Role of AT-406 as a SMAC Mimetic in Cancer

Abstract

Endogenous SMACs are mitochondrial proapoptotic proteins that suppress the inhibitors of apoptosis proteins IAPs . Inhibitors of apoptosis proteins are highly expressed at many human cancers. Small molecule inhibitors of the inhibitors of apoptosis proteins mimicking the endogenous inhibitors of apoptosis proteins antagonist second mitochondria-derived activator of caspases are called SMAC mimetics. AT-406 that effectively targets XIAP and cIAP-1/2 is an orally active SMAC mimetic. It is stated that it highly efficiently inhibits the development of cancer cells in research related to various human cancer cell lines. It has been shown to induce apoptosis in xenograft tumor research in vivo in mice, rats, non-human primates and dogs. AT-406 has recently been investigated in phase I/II clinical trials for the treatment of human cancer. Our aim in this review was to present the research performed on AT-406 in various types of cancer cells

Keywords

• AT-406, SMAC mimetic, IAP proteins, Anticancer, Proapoptotic

SMAC Mimetiği Olarak AT-406?nın Kanserdeki Rolü

Öz

Endojen ikinci mitokondri kökenli kaspaz aktivatörleri SMAC , apoptozis inhibitör proteinleri IAPs ’ni baskılayan mitokondriyal pro-apoptotik proteinlerdir. Apoptozis inhibitör proteinleri bir çok insan kanserlerinde yüksek seviyede eksprese edilmektedir. Endojen apoptosis inhibitör proteini antogonisti ikinci mitokondri kökenli kaspaz aktivatörlerini taklit eden apoptosis inhibitör proteininin küçük moleküllü inhibitörleri SMAC mimetikleri olarak adlandırılır. AT-406, XIAP’ı ve cIAP-1/2’yi etkili şekilde hedefleyen oral olarak aktif bir SMAC mimetiğidir. Çeşitli insan kanser hücre hatları ile ilgili araştırmalarda kanser hücresi gelişimini yüksek etkinlikle baskıladığı belirtilmektedir. Fare, sıçan, insan olmayan primatlarda ve köpeklerde yapılmış in vivo ksenograft tümör araştırmalarında apoptozisi indüklediği gösterilmiştir. Günümüzde AT-406, insan kanser tedavisi için faz-I/II klinik denemelerinde araştırılmaktadır. Derlemede, AT-406 ile yapılmış farklı kanser hücre tipleriyle ilgili çalışmalar hakkında bilgiler verilmesi amaçlanmıştır

Anahtar Kelimeler

• AT-406, SMAC mimetiği, IAP proteinleri, Antikanser, Proapoptotik

Kaynakça

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