Proteolysis Targeted Chimera “PROTAC”

Abstract

As an emerging therapeutic strategy, Proteolysis Targeted Chimera (PROTAC) is a bifunctional molecule that leads to degradation rather than inhibition of the activity of a specific target protein. PROTAC molecules consist of three parts, a target protein ligand, E3 ligase, and a linker, and use the ubiquitin proteosome system in the cell to cleave different target proteins. PROTAC technology has advanced significantly in the last two decades and has become a breakthrough in cancer treatment by attracting attention today. While the PROTAC approach is also causing a devastating change in drug discovery studies, the many potential advantages and extraordinary challenges that lie ahead of this technology are discussed. In this review, information on the advantages and challenges of PROTAC that will contribute to cancer treatment and drug discovery studies is given by comparing it with traditional and modern treatment methods.

Keywords

• PROTAC
• UPS
• Drug discovery
• Cancer treatment

Kanser Tedavisinde Yeni Bir Yaklaşım “Proteoliz Hedefli Kimera”

Abstract

Gelişmekte olan terapötik bir strateji olarak Proteoliz Hedefli Kimera (PROTAC), belirli bir hedef protein aktivitesinin inhibisyonundan ziyade, degredasyonuna yol açan iki işlevli bir moleküldür. PROTAC molekülleri, bir hedef protein ligandı, E3 ligaz ve bir bağlayıcı olmak üzere üç kısımdan oluşmakta ve farklı hedef proteinleri parçalamak için hücredeki ubikutin proteozom sistemini kullanmaktadır. PROTAC teknolojisi, son yirmi yılda önemli ölçüde ilerlemiş ve günümüzde de dikkatleri üzerinde toplayarak kanser tedavisinde çığır açabilecek bir dönüm noktası haline gelmiştir. PROTAC yaklaşımı aynı zamanda ilaç keşif çalışmalarında yıkıcı bir değişikliğe sebep olmakla birlikte bu teknolojinin önünde yatan birçok potansiyel avantaj ve olağanüstü zorluklar tartışılmaktadır. Bu derlemede, PROTAC’ın geleneksel ve modern tedavi yöntemleri ile karşılaştırılarak, kanser tedavisine ve ilaç keşif çalışmalarına katkı sağlayacak avantaj ve zorluklarına yönelik bilgilere yer verilmektedir.

Keywords

• PROTAC
• UPS
• İlaç keşfi
• Kanser tedavisi

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