Focused library for probing the kinase cysteinome
240 compounds
Our library is designed to unlock new opportunities in kinase drug discovery by targeting cysteine residues in or proximal to ATP-binding pocket. Unlike traditional non-covalent approaches, covalent fragments offer the advantage of enhanced selectivity and durable inhibition across highly structurally similar kinases.
This library was built using a generalizable strategy to sample accessible cysteines across the kinome, incorporating fragment-like electrophiles optimized for covalent engagement. Inspired by the work of the research groups of Prof. Stefan Knapp and Prof. Matthias Gehringer, published in Angew. Chem. Int. Ed. 2025, 64, e202419736, we expanded the original 47-fragment research library into a collection of 240 compounds. The published study identified promising hits against kinases and cysteine positions that had not previously been targeted covalently. The resulting library is a high-quality, kinase-focused covalent fragment collection that expands the repertoire of targetable cysteines and provides powerful starting points for developing highly potent, selective covalent inhibitors.
Typical Formats
Catalog No.
KCF-240-0-Z-2
Compounds
240
1 plate
Amount
≤ 300 nL of 2 mM DMSO solutions
Plates and formats
1536 well, Echo Qualified 001-6969 (LP-0400), first four and last four columns empty, 1280 compounds per plate
Price
Catalog No.
KCF-240-10-Y-100
Compounds
240
1 plate
Amount
10 µL of 100 mM DMSO solutions
Plates and formats
384 well, Echo Qualified LDV microplates 001-12782 (LP-0200), first and last two columns empty, 320 compounds per plate
Price
Catalog No.
KCF-240-50-Y-20
Compounds
240
1 plate
Amount
50 μL of 20mM DMSO solutions
Plates and formats
384 well, Greiner Bio-One microplates 781280, first and last two columns empty, 320 compounds per plate
Price
*We will be happy to provide our library in any other most convenient for your project format. Please select among the following our standard microplates: Greiner Bio-One 781270, 784201, 781280, 651201 or Echo Qualified 001-12782 (LP-0200), 001-14555 (PP-0200), 001-6969 (LP-0400) or send your preferred labware. Compounds pooling can be provided upon request.
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Key features
- Acrylamide warhead only
- Hinge-binder scaffolds
- Kinetic profiling and controlled reactivity toward thiols
Library design
As described in Angew. Chem. Int. Ed. 2025, 64, e202419736 systematic screening against a curated panel of 47 kinases, covering 60 active-site proximal cysteines, has already demonstrated unique binding modes and isoform-specific hits validated by LC/MS, DSF, and crystallography. Compounds in the library have a modular structure and contain three parts: a hinge-binding fragment, a linker, and an acrylamide warhead. Our library includes 45 originally reported fragments and 195 additional fragments designed using a similar methodology and synthesized by our chemists to broaden the range of hinge binders, linkers, and possible acrylamide positions.
Fig. 1. a) Design principles of the fragments for targeting kinase cysteines near hinge region b) Cysteine residue positions potentially amenable to covalent targeting (picture from Angew. Chem. Int. Ed. 2018, 57, 4372.)
Examples of kinase covalent fragments
Molecular properties
