Glutamic Acid–Valine–Citrulline (EVCit) Linker: Enhancing ADC Stability and Effectiveness
Overview of ADCs
Antibody–drug conjugates (ADCs) are revolutionizing cancer treatment by combining monoclonal antibodies with potent cytotoxic drugs. FDA-approved ADCs like Adcetris® and Kadcyla® have shown significant clinical success. However, the effectiveness of ADCs depends heavily on the choice of linker used to attach the drug to the antibody.
Challenges with Traditional Linkers
Valine–citrulline (VCit) linkers are popular for their ability to release drugs upon reaching target cells. Despite this, VCit linkers are unstable in mouse plasma due to hydrolysis by carboxylesterase 1c (Ces1c), leading to premature drug release and unreliable preclinical results.
Introducing EVCit Linker
The glutamic acid–valine–citrulline (EVCit) linker addresses the stability issues of VCit linkers:
- Enhanced Plasma Stability: EVCit linkers maintain stability in both mouse and human plasma, minimizing premature drug release.
- Effective Payload Release: EVCit still allows for efficient drug release inside target cells through cathepsin-mediated cleavage.
- Improved Efficacy: ADCs with EVCit linkers show superior antitumor effects in preclinical models compared to those with VCit linkers.
Key Benefits of EVCit Linkers
- Greater Stability: Reduces the risk of early drug release, improving the accuracy of preclinical evaluations.
- Reliable Payload Delivery: Ensures effective release of the drug inside target cells.
- Enhanced Therapeutic Performance: Demonstrates better efficacy in animal models, offering promising results for future clinical applications.
- Versatile Application: Suitable for a range of molecular drug conjugates beyond ADCs.
Conclusion
Ref:
Anami, Y., Yamazaki, C.M., Xiong, W. et al. Glutamic acid–valine–citrulline linkers ensure stability and efficacy of antibody–drug conjugates in mice. Nat Commun 9, 2512 (2018). https://doi.org/10.1038/s41467-018-04982-3.
AxisPharm maintain Fmoc-EVCit-PAB linker in stock and can custom synthesize corresponding pegylated EVCit-PAB linker with competitve price.
AxisPharm offers 5000+ PEG Linkers with high purity. Different kinds of PEG Reagents may be available by custom synthesis.
