Ligand Design for Akt-targeting PROTAC^®

Creative Biolabs is a professional CRO company that has developed a comprehensive service chain in developing various kinase-targeting PROTAC^® (proteolysis targeting chimera) for disease therapy. With in-depth expertise in Akt structural analysis, we have successfully completed several ligand design projects in this filed which can help our worldwide customers shorten the drug development time and offer the most meaningful data.

Introduction to Akt

Protein kinase B, also known as Akt, is a member of the AGC subfamily that plays an important role in mediating cell metabolism, cell transcriptional activity, and cell death. Three subtypes of Akt, Akt1, Akt2, and Akt3, have been cloned and identified in human. Previous studies have shown that these subtypes have a highly conserved structure that contains three biological activity domains, including the pleckstrin homology (PH) domain at the N-terminal, the functional regulation region at the C-terminal, and the key kinase domain. Meanwhile, Akt has been regarded as a key regulator for PKB/Akt signaling pathway in various disease progression. Moreover, researchers have demonstrated that the disruption of the Akt pathway is strongly related to many cancer progression. The down-regulation expression of Akt is usually found in almost all cancer types. In addition, it has been reported that inhibition of Akt by PROTAC^® technology will reduce the cell apoptotic threshold and kill cancer cells. As a result, Akt has become a perfect target for cancer therapy.

Fig.1 Approach to PROTAC^® development. (Lai, 2016)

Our Ligand Design Platform for Akt-targeting PROTAC^®

Akt is a critical functional molecule that is responsible for mediating the signal transduction activity in many pathways, and its dysregulation will lead to a number of human diseases. In the past few years, strenuous efforts have been made to discover novel ligands for Akt. Its ligands can inhibit the kinase-dependent and kinase-independent activity by reducing the expression level of target proteins to offer therapeutic intervention.

Currently, PROTAC^® technology is widely used for designing Akt-targeting ligands in recent studies. As a professional service provider in ligand design, Creative Biolabs has established a comprehensive Akt-targeting ligand design platforms to help our client design, optimize and assess different ligands, such as small-molecule-based ligands, peptide-based ligands, as well as antibody-based ligands. In addition, our mature PROTAC^® technology has been established to develop chimeric degraders. In a recent study, we have successfully developed a specific degrader to induce Akt kinase degradation, indicating that Akt-targeting PROTAC^® is a flexible and effective tool for designing or modifying kinase and its ligands.

Creative Biolabs is a leading custom service provider in the field of ligand design for PROTAC^®. We can provide many flexible options, from which you can always find a better match for your particular project. Please feel free to contact us for closer communication to learn how we can be involved in your project. Separate services or integrated end-to-end solutions are all welcomed.

Reference

1. Lai, A. C.; et al. Modular PROTAC^® Design for the Degradation of Oncogenic BCR-ABL. Angew Chem Int Ed Engl. 2016, 55(2): 807-10.