In modern drug discovery, reliable access to well-characterized reference materials is essential for accelerating research and ensuring reproducibility.

Enamine is proud to collaborate with Pfizer to bring to the scientific community an authentic collection of reference compounds directly through our Enamine marketplace and Enamines integration capabilities (i.e. punchout site, hosted catalogs, and API solutions).

This allows researchers to explore and purchase from the catalog of selected Pfizer-provided drugs, chemical dormants, investigational compounds, and isotope-labelled molecules with appropriate quality control.

Together, Pfizer Reference Compounds and Enamine global infrastructure create a powerful resource for advancing science. Researchers can now explore new chemical space, validate findings against authentic benchmarks, and push forward the boundaries of medicinal chemistry.

Acrylamides are the most popular covalent warheads present in approved drugs. α-Cyanoacrylamides are a novel class of electrophilic warheads currently under active investigation in the field of covalent drug discovery. They combine moderate reactivity with high selectivity, making them an attractive alternative to irreversible warheads such as acrylamides or vinyl sulfones. Due to the presence of an electron-withdrawing cyano-group, Cyanoacrylamides are capable of forming reversible covalent bonds with nucleophilic residues, particularly the thiol groups of cysteine. This enables controlled residence time and helps to reduce the risk of off-target effects.

Cyanoacrylamide warheads have already been applied in a number of promising compounds, especially for kinase targeting, such as FM409 and PRN1008 (BTK inhibitor). Cyanoacrylamides can also be used for other targets, such as Chst15. An example of a related compound, Entacapone, has been approved for the treatment of Parkinson’s disease.

Enamine has almost 5k compounds in stock (90%+ pure by LCMS and/or NMR analysis), which can be delivered as dry powders or in any customized plated formats. Access to our extensive building block inventory, combined with validated synthetic approaches, enabled the creation of a 19-million-compound REAL Cyanoacrylamide Array. Compounds from this array can be synthesized within 3–4 weeks in our parallel synthesis department, with an on-time delivery rate exceeding 80%.

Explore our pre-plated Cyanoacrylamide fragments and screening libraries—ready for immediate use.

Cyanamides, also known as N-nitriles, have recently emerged as promising electrophilic warheads in covalent drug discovery, offering a balance between reactivity and selectivity. Their moderate electrophilicity makes them attractive alternatives to more reactive groups like acrylamides or vinyl sulfones. Cyanamides have also been explored for their ability to engage in reversible binding, forming isothioureas, which can be beneficial in certain applications.

Cyanamide-based inhibitors have been applied in targeting kinases, such as BTK, and even viral proteases. Recent studies have demonstrated that cyanamides can be engineered to attain high selectivity. For instance, N-cyanopiperazines were shown to covalently and selectively inhibit the deubiquitinating enzyme UCHL1, avoiding off-target effects on closely related enzymes like PARK7.

Cyanamide reversible binding to Cys-residues

We offer over 700 cyanamide compounds as dry powders and have designed a pre-plated library of 240 compounds. Covalent Screening N-nitriles Library is available in a pre-plated format at 10 mM concentration in DMSO. It can be purchased either as a standalone set or as a sublibrary of Covalent Screening Library.

Enamine unREAL^® Space is a new, original extension to Enamine REAL compounds.
This collection is broad and diverse, opening a much larger access to synthetically accessible chemical space for drug discovery. All compounds from the unREAL Space are available in the shortest possible time thanks to well-established and validated synthesis protocols. The unREAL Compounds are assembled using 24 unique, well-validated synthetic protocols not included in the REAL/xREAL Space.