Kinase Hinge Binders Library

Kinase inhibitors have become a clinically important family of prescription drugs that are part of targeted therapies, and kinase inhibitors are widely used in the immunology area to treat arthritis. The most direct and easiest approach to the design of kinase inhibitors is to target the ATP pocket, which is located inside the deep cleft between the two structural domains of the kinase. The hinge is a single string of the amino acid segments that connects the two structural domains. Among the 23 kinase inhibitors that have entered the market to date, most of them are kinase ATP-binding pocket inhibitors, and this type of inhibitor can be considered as an ATP mimetics because they interact similarly to that of ATP.

BOC Sciences has focused on studying and designing the hinge-binding agents required for kinase ATP-pocket inhibitors. Our hinge binders can form one to three hydrogen bonds with the hinge, and be able to recognize potential inhibitors that target the ATP pocket.

Kinase Hinge Binders 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, we comprehensively analyze molecular fragments capable of forming at least two hydrogen bonds with hinge regions and developed appropriate topological models to search for directed inhibitors
2. The screening model is then evaluated using a set of known kinase inhibitors (over 2,000 molecules with high inhibitory activity)
3. In this step, the validated topological model is applied to our HTS compound collection to generate the kinase hinge binders library
4. Finally, the resulting set of compounds are evaluated with main focus on novel chemotypes. Moreover, the compounds obtained will be further filtered using Lipinski's Rule of Five to deliver only drug-like ones. PAINS compounds and compounds with reactive groups are removed from the library

Figure 1. Discovery of a novel kinase hinge binder fragment by dynamic undocking. (Rachman, M.; et al. 2020)

Kinase Hinge Binders Library Characteristics

• We carefully design hinge binders containing one to multiple functional groups at different positions that can be sequentially derived
• Our experts also add compounds with substituents such as methyl, trifluoromethyl, methoxy or trifluoromethoxy adjacent to the functional groups in order to change the conformation
• 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 Kinase Hinge Binders Library design at competitive prices for global customers. Personalized and customized services of Kinase Hinge Binders 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!