Small Molecule Inhibitors Targeting RNA Modifying Enzymes to Modulate Drug Response and Overcome Drug Resistance

SUMMARY

• DNA hypomethylating agents have been widely used to treat various hematologic and non-hematologic malignancies. However, accumulating evidence has demonstrated that DNA methylation status does not correlate with clinical response to hypomethylating agents. 
• Two RNA cytosine methyltransferases (RCMTs) NSUN1 and NSUN2 are responsible for catalyzing the majority of 5-methylcytosine in RNA (RNA:mC) and regulate chromatin structure, gene expression and organelle functions in human cells.  NSUN1 and NSUN2 are correlated with a significant shorter survival in almost all cancer subtypes. 
• The faculty inventor has developed small molecule inhibitors that target RCMTs NSUN1 and NSUN2-mediated active chromatin structures (ACS) to overcome cancer drug resistance.   
• Additionally, the inventor established a novel fluorescence quenching complex and NSUN1/2-ACS-targeting NSUN1/2ACS/FQRA plate assay for high-throughput drug tests and screening. 

FIGURE

ADVANTAGES

ADVANTAGES

• New mechanisms of action to overcome drug resistance

• Novel biological anticancer activities

• Novel fluorescent quenching complex

APPLICATIONS

• Therapeutic alternatives for overcoming cancer drug resistance

• Quickly predict drug resistance

• High-throughput drug tests and screening

September 11, 2023

Proof of concept

Patent Pending

Licensing,Co-development

Jason Cheng