NETWORK-BASED ANALYSIS OF PROTAC COMPOUNDS TARGETING CDK4/6 IN BREAST CANCER: IDENTIFICATION OF GENE INTERACTIONS AND THERAPEUTIC INSIGHTS

Abstract

Cancer is a major disease characterized by rapid and uncontrolled cell growth and proliferation, affecting a large population worldwide. A significant portion of cancer research today involves network analysis. In this study, the gene targets of 8-Cyclopentyl-2-(4-piperazin-1-ylanilino) pteridin-7-one (CPPP-7-one) and the PROTAC CDK4/6 degrader (PROTAC-CDK4/6i) were identified, and their shared targets with breast cancer-related genes were examined. Additionally, protein-protein interactions (PPI) involving the gene targets of these compounds were mapped. The analysis revealed that CDK4 is a common gene target between breast cancer and the CPPP-7-one compound. In contrast, GRM2, the sole gene target of the PROTAC CDK4/6 degrader, did not overlap with any breast cancer-related genes. These findings suggest that CPPP-7-one may play a significant role in cyclin and cyclin-dependent kinase activities, particularly in regulating cell cycle checkpoints, and therefore warrants further investigation. Furthermore, the isolated nature of PROTAC CDK4/6i's target from core cell cycle proteins indicates that it may influence distinct intracellular mechanisms.

Keywords

• Breast Cancer
• PPI network analysis
• CDK
• PROTAC

MEME KANSERİNDE CDK4/6'YI HEDEFLEYEN PROTAC BİLEŞENLERİNİN AĞ TABANLI ANALİZİ: GEN ETKİLEŞİMLERİNİN BELİRLENMESİ VE TERAPÖTİK ÖNGÖRÜLER

Abstract

Kanser hızlı ve kontrolsüz hücre büyümesi ve çoğalması olarak tanımlanan ve çok geniş kitleleri etkileyen önemli bir hastalıktır. Kanser üzerinde yapılan araştırmaların önemli bir bölümünü network analizleri oluşturmaktadır. Yapılan bu çalışmada 8-Cyclopentyl-2-(4-piperazin-1-ylanilino) pteridin-7-one (CPPP-7-one) ve PROTAC CDK4/6 degrader (PROTAC-CDK4/6i) bileşenlerinin gen hedefleri bulunmuş, meme kanseri hedefleri ile ortak genleri tespit edilmiştir. Ayrıca bileşenlerin gen hedeflerini protein-protein (PPI) etkileşimleri bulunmuştur. Yapılan bu analizlerin sonucunda meme kanseri ile CPPP-7-one bileşiğinin CDK4 geni ortak olarak bulunmuştur. PROTAC CDK4/6 degrader bileşiğinin GRM2 gen tek gen hedefi meme kanseri ile ortak gen içermemektedir. Sonuç olarak CPPP-7-one bileşiğinin özellikle siklinler ve siklin bağımlı kinaz aktivitelerinde etkili olduğu, hücre döngüsü kontrol noktalarını etkilediği için daha geniş çapta araştırılmasına ihityaç vardır. PROTAC CDK4/6 degrader bileşiğinin de hücre döngüsü proteinlerinden izole olması hücre içinde daha farklı mekanizmaları etkilediğini göstermektedir.

Keywords

• Meme kanseri
• PPI network analizleri
• CDK
• PROTAC

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