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Covalent Screening Library

The library of compounds with diverse covalent "warheads"

21 969 compounds

Covalent modifiers have attracted much attention in recent years; over 30% marketed drugs have this mode of action. The increased biochemical potency associated with an irreversible mechanism can actually lead to increased therapeutic profitability, as lower drug concentrations are required for effectiveness. Nevertheless, design of selective covalent modifiers is a difficult task since it is difficult to find the right balance between reactivity and selectivity.

Most popular library formats

Item
Catalog No.
Compounds
Plates
Amount
Format

Item

1

Catalog No.

CSL-14-Y-0

Compounds

14 249

Plates

45

Amount

150 nL of 2 mM DMSO solutions

Format

384-well microplates, 320 cpds per plate,
first two and last two columns empty

Item

2

Catalog No.

CSL-14-Z-10

Compounds

14 249

Plates

12

Amount

10 µL of 10 mM
DMSO stock solutions

Format

1536-well microplates, Echo Qualified,
1280 cmpds per plate, first four and last four columns empty

Item

3

Catalog No.

CSL-14-Y-25

Compounds

14 249

Plates

45

Amount

25 µL of 10 mM
DMSO solutions

Format

384-well microplates, 320 cpds per plate,
first two and last two columns empty

Library design

Enamine Covalent Screening Library has been extracted from the "Rule of Five" compliant subset of the Screening Collection using substructure searches of specified structural features. Active functionalities able to form covalent bonds with protein residues have been analyzed, and the “warheads” listed below were selected as optimal in terms of reactivity and essential stability. Additionally, the chemical environment of each reactive group was checked to be suitable for moderate reactivity of the compound. Molecules with non-druglike cores and structural features were removed from the library using internal structure filters and in-house elaborated rules. The final set of selected compounds has been evaluated manually to avoid too reactive entities and eliminate structural shortcomings of the substructure searches.

Structural fragments used for the selection

  • Acrylamides, acrylonitriles
  • Activated terminal acetylenes
  • Cloracetamides, Alkyl halides
  • Epoxides, aziridines
  • Alkyl thioles, disulfides
  • β-lactams, -lactones
  • Sulfonyl fluorides/esters
  • Carbamates, activated Aryl ureas
  • 2-cyano/-Cl nitrogen heterocycles
  • Vinylsulfones, -sulfonamides
  • Boronic acids

General scheme of the library design

Examples of the compounds

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