Specific Covalent Inhibitor Fragment Library

Covalent inhibitors and non-covalent inhibitors are two types of inhibitors that target biological targets. At present, most small molecule drugs are still non-covalent inhibitors which can reversibly bind to biological targets. The affinity between them and the target often determines the therapeutic effect of the drug. Therefore, the goal of research and development of small molecule drugs discovery is to identify compounds that can bind to biological targets with high affinity. After the covalent inhibitor binds to the biological target, the group on the compound can chemically react with the target to form a covalent bond which allows the covalent inhibitor to form a stable complex with the target protein, thereby irreversibly inhibiting the activity of the target protein. BOC Sciences can design a Specific Covalent Inhibitor Fragment Library, which contain compounds with specific reactive moieties (such as acrylamide, vinyl sulfone and vinyl sulfonamide groups).

Figure 1. A historic overview of covalent inhibitors and their approval dates. The warheads are highlighted in red. (Sutanto, F.; et al. 2020)

Advantages of Specific Covalent Inhibitor

• Specific covalent inhibitors can irreversibly inhibit the activity of the target protein, which means that the covalent inhibitor can maintain the inhibitory effect before the cell produces a new target protein
• Specific covalent inhibitors only need fewer doses to achieve the same curative effect as non-covalent inhibitors
• Compared with non-covalent inhibitors, specific covalent inhibitors have more advantages in targeting targets that are prone to resistance.

Figure 2. Chemical structures and binding modes with the target protein: (a) AMG510 and (b) MRTX-849. (Sutanto, F.; et al. 2020)

Advanced Covalent Warhead

BOC Sciences is committed to offering advanced covalent warhead to construct our high quality Specific Covalent Inhibitor Fragment Library. The following ‘warheads’ are used for substructure searches of the compounds to be included in the library:

Table1. The summary of the BOC Sciences Specific Covalent Inhibitor Fragment Library characteristics

Features of Specific Covalent Inhibitor Fragment Library

• A wide range of chemical structure dissimilarity and are compliant with in-house PAINS structural filters
• All compounds are filtered according to the the well-known Rule of Three criteria
• A variety of physical and chemical parameters and medicinal chemical structure filters are applied to design our unique Specific Covalent Inhibitor Fragment Library
• Choose warheads carefully: only experimentally confirmed reactivity, reported in the literature
• Around 600 structurally diverse compounds bearing carbon-carbon double bonds activated by either carbonyl or sulfo groups are extracted from our HTS Compound Collection
• All compounds can be used for cherry-picking

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
• Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Specific Covalent Inhibitor Fragment Library design at competitive prices for global customers. Personalized and customized services of Specific Covalent Inhibitor Fragment 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!