The Cys-focused Screening Compound Library was created on the basis of specific structure moieties that could react reversibly or irreversibly with cysteine residues of a drug target. It contains over 3,400 potential covalent modifiers.
On the basis of literature data [1-8], 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. Michael 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.
Covalent inhibitors 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 selection of potential cysteine covalent binders for covalent screening efforts.
The compound selection can be customized based on your requirements, cherry-picking is available. A pre-plated set based on this Screening Library is also offered. For more details, please, consult our Pre-plated Focused Libraries. Please, contact us at email@example.com for any additional information and price quotations.
Figure 1. Covalent warheads distribution for compounds in the Cysteine-focused Covalent Inhibitor Library
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