This Cysteine-focused Screening Compound Library contains 13,900 potential covalent modifiers, containing specific structure moieties that could react with cysteine residues of a drug target reversibly or irreversibly.
We selected the most important functional groups that are known to target binding pockets of proteins through the formation of covalent bonds with cysteine amino acid residues based on available literature data [1-8]. Michael's acceptors are typical functionalities that are often introduced in structures of this type of covalent inhibitors, as well as fragments, capable of nucleophilic displacement or addition.
Covalently binding molecules focused on Cys residue were selected from the Life Chemicals HTS Compound Collection, employing the following covalent warheads (Fig. 1):
- α,β-unsaturated ketones
- activated acetylenes
- methyl vinylsulfones
- phenylsulphonate esters
- aminomethyl methyl acrylathes
- primary haloalkanes
The compounds were pre-filtered with the Rule of Five restrictions:
- MW 150 - 500
- ClogP -1 - 5
- H-donors 0 - 5
- H-acceptors 0 - 10
- Rotatable bonds ≤ 10
Subsequently, machine learning methods (such as covalent fingerprints) and diversity filtering were applied to refine the full selection of potential cysteine covalent inhibitors to provide the Cys-focused Diversity Screening Set of over 3,800 drug-like cysteine covalent binders for covalent screening efforts in drug discovery.
The compound selection can be customized based on your requirements, cherry picking is available.
Please, contact us at firstname.lastname@example.org for any additional information and price quotations.
For a pre plated set based on this Screening Library, please explore our Pre-plated Focused Libraries.
Figure 1. Covalent warhead distribution for compounds in the Cysteine-focused Covalent Inhibitor Library
Figure 2. Covalent warhead distribution for compounds in the Diversity Screening Set of the Cysteine-focused Covalent Inhibitor Library
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