Developing a CITK Protein Degrader Using the QuicTPD™ Platform

WEBINAR

The orphan citron rho-interacting kinase (CITK) is a protein that plays a fundamental role in cell division and, consequentially, is promising for potential cancer drugs like proteolysis targeting chimeras (PROTACs), which could destroy these problem proteins. Researchers as the Cleveland Clinic Center for Therapeutics Discovery recently developed C3TD879, an inhibitor molecule developed specifically to block CITK’s activity. While this is a promising first step in developing an effective PROTAC to fight cancer, simply inhibiting CITK’s activity didn’t fully replicate what happens when CITK was genetically deleted in previous experiments. This suggests that CITK could have additional, non-enzymatic roles in cell division and highlights the importance of trial-and-error in developing PROTACs.

In this webinar, our expert guests will demonstrate their solution for PROTAC drug discovery: the QuicTPD™ ’direct-to-biology’ platform. The platform uses a high-throughput 96-well plate system to speed up the entire process of making and testing PROTACs– from chemical design to biological evaluation.

Key learnings

• The dual catalytic and scaffolding functions of multidomain proteins, especially kinases
• The importance of shotgun direct-to-biology approaches as a rapid strategy for PROTAC lead ID where predictive algorithms for selecting a partner E3 and linker geometry are still not confident enough for routine use
• How to establish a robust testing funnel prior to embarking on synthesis of PROTACs, particularly with respect to NanoBRET assays as well as HiBiT-tagged cell lines