Covalent Heterocyclic Fragment Library for identification of Cryptic and Allosteric Pocket
141 compounds
This unique library of small heterocyclic electrophiles developed by the research group of Prof. György Keserű have been shown to be effective in finding tiny new binding pockets for different protein targets (MedChemComm 2019, Nat. Commun. 2020 and Pharmaceuticals 2022). The library combines the advantages of Astex’s MiniFrags in exploring unprecedented binding site with that of covalent binders in higher affinity and easier detection. It consists of six and five-membered heterocycles most abundant in drugs that are equipped with only one or two-atom covalent warheads. This makes it unique in contrast to those often used in covalent screening, much larger acrylamides and chloroacetamides which can significantly influence the binding mode of active molecules. Thus, applying the smallest possible covalent function helps to avoid promiscuity and keep the same recognition pattern of non-covalent scaffolds.
On the other hand, the electrophile-first approach proved to be an effective way of developing covalent drugs (Nat. Rev. Drug Discov. 2022). A number of covalent probes and drug candidates, including recent examples of Nirmatrelvir and Sotorasib have been developed using covalent screening techniques.
Covalent MiniFrags is a unique tool for searching of new binding pockets, elaboration of discovered hits and growing vector identification. The XChem facility at Diamond LightSource UK is a strategic partner in pioneering applications of Covalent MiniFrags.
Typical Formats
Catalog No.
CMF-141-5-Y-500
Compounds
141
1 plate
Amount
5 μL of 500 mM DMSO solutions
Plates and formats
384-well acoustic LDV plates, first two and last two columns empty
Price
Catalog No.
CMF‑141‑25‑X‑100
Compounds
141
2 plates
Amount
25 μL of 100 mM DMSO solutions
Plates and formats
96-well plates, Greiner Cat. No 650201, round (U) bottom, 1 & 12 columns empty, 80 compounds per plate
Price
Catalog No.
CMF‑141
Compounds
141
Amount
Custom
Plates and formats
Any custom format
Price
Download SD files
Key features
- Most common nitrogen-containing heterocycles
- The smallest covalent warheads
- Experimentally characterized stability and intrinsic reactivity
- Evaluated on a number of targets
Covalent MiniFrags Library consists of 85 heterocyclic electrophiles and 56 N-methylated functional heterocycles. Both subsets are described in detail in scientific publications and are now available for your research.
