Allosteric Kinase Library

Small molecule kinase inhibitors are essential targeted therapeutic agents for the treatment of various human diseases, particularly cancer. Although most of small-molecule inhibitors are targeting ATP-binding kinase pockets, the significant sequential and structural similarities among ATP pockets make selective inhibition of kinases a great challenge. However, allosteric inhibition of kinase signaling is a useful approach to obtain the inhibitors with specific selectivity. Moreover, the allosteric kinase inhibitors are able to overcome resistance of the orthosteric ATP-binding sites. The development of allosteric kinase inhibitors that bind outside the structural domain of the catalytic kinase has offered unique opportunities in this field. Scientists have provided new strategies to develop specific kinase inhibitors by targeting binding pockets adjacent or non-adjacent to the ATP binding pocket.

BOC Sciences is committed to establishing a unique library to deliver potential allosteric kinase inhibitors.

Library Design

Based on detailed structural analysis of the known and most potent kinase inhibitors, BOC Sciences has developed a series of unique structural filters that are designed to identify potential inhibitors targeting the ATP pocket.

1. Firstly, our medicinal chemists comprehensively analyze all available structures with kinase allosteric inhibitors

We identify the following four possible allosteric kinase pockets:

• Myristoyl pocket
• Inhibitor binding mode that occupies part of the binding pocket adjacent to the ATP-site
• PIF-pocket (regulatory site targeted)
• Relative allosteric regulators of pocket-type I^1/2 kinases
2. Then, we select representative protein-ligand complexes to perform molecular docking, while a filtering is carried out against our HTS compound collection to search for potential inhibitors
3. In this step, we use the reference sets of actives to validate the compounds obtained from the last step, and then a flexible molecular docking is conducted to target several protein models
4. Finally, over 5,000 promising allosteric kinase inhibitors can be generated successfully

Figure 1. Allosteric inhibition of kinase signaling. (Xiao, L.; et al. 2020)

Allosteric Kinase Library Characteristics

• Favorable physicochemical parameters and solubility requirements
• No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
• Bioactivity and safety confirmed by preclinical studies and clinical trials
• Structural diversity, medicinal activity, and cellular penetration
• Structural document, IC₅₀, and other chemical and biological data are provided
• All compounds are continually updated
• Compound cherry-picking service is provided

What We Deliver

• Delivered within 2 weeks in any customer-preferred format
• Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
• All compounds have a minimum purity of 90% assessed by ¹H NMR and HPLC
• Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Allosteric Kinase Library design at competitive prices for global customers. Personalized and customized services of Allosteric Kinase Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!