For Research Use Only. Not for Clinical Use.

Creative Biolabs has long-lasting expertise in the design and conduct of novel drug molecules. Based on our advanced platforms and extensive experience, now we can provide XTEN-based half-life extension services for our clients all over the world.

Introduction of XTEN

In recent years, increasing molecular size to reduce renal clearance has been proven to be an effective way to extend the half-life of drugs, and linking drugs to XTEN is the most common strategy to increase molecular size. Composed of six hydrophilic and chemically stable amino acids A, E, G, P, S, and T, XTEN polymers are a class of unstructured polypeptides. The extended and unstructured conformation of XTEN allows a large hydrodynamic volume. For example, XTEN864 refers to the XTEN polymer containing 864 amino acids. From aa288 to aa864, longer XTEN peptides represent greater hydrodynamic volume, resulting in lower renal clearance and longer half-life. Experimental data showed that XTEN864-protein exhibits a half-life that is approximately 10 times longer than XTEN288-protein. With a variety of advantages, including low immunogenicity and well-tolerated, XTEN polymer has been served as a promising half-life extension strategy for drug development.

Fig 1. XTENylation of biologically active molecules. (Podust, 2016)

Applications of XTEN in Half-Life Extension

Therapeutic peptides and proteins present great potentials for diseases treatment but are always limited by the short half-life. To solve this problem, multiple unstructured polypeptides have been used to extend drug half-life. Nowadays, there are a series of clinical trials in progress for XTEN-based therapeutics modification. For the treatment of type 2 diabetes mellitus, the half-life of the drug construct formed by coupling exendin-4 with XTEN864 can be increased to 128 hours in humans. The complex protein FVIIIFc-VWF-XTEN presents a 2-fold improvement in pharmacokinetic properties compared to rFVIII-Fc. What’s more, XTEN polymers have been widely applied as a carrier to extend the half-lives in multiple proteins and peptides, such as glucagon, GLP-2, coagulation factors VIIa, VIII, and IX, as well as others.

Advantages of XTEN Based Half-Life Extension

• Flexibility: The half-life of the payload can be adjusted by adjusting the length of the XTEN polymer.
• Safety: XTEN polymer can be completely degraded in the kidney to avoid accumulation in tissues.
• Low immunogenicity
• Well-tolerated

Creative Biolabs has been a long-term expert in the field of drug development, we offer a variety of solutions to fit your specific research needs. If you are interested in our products or services, please do not hesitate to contact us for more detailed information.

XTEN Based Half-Life Extension Service FAQs

Reference

1. Podust, V.; et al. Extension of in vivo half-life of biologically active molecules by XTEN protein polymers. Journal of Controlled Release. 2016, 240: 52-66.