4 929 compounds in stock and over 19M in REAL
800 compounds pre-plated Covalent Fragments Cyanoacrylamides Library
1 920 compounds pre-plated Covalent Screening Cyanoacrylamides Library
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.
Typical Formats
Catalog No.
CACR-800-10-X-100
Compounds
800
3 plates
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.
CSCA-1920-50-X-10
Compounds
1 920
6 plates
Amount
50 µL of 10 mM DMSO solutions
Plates and formats
384-well, Greiner Bio-One plates #781280, 1,2 and 23,24 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.
Hits derived from this library can be easily followed with analogues from stock or either synthesis of new compounds from REAL.
Download SD files
4 929 compounds for cherry-picking
Plated libraries in stock:
Library code: CSCA-1920
Version: 20 February 2023
1 920 compounds
Key features
- Reversible covalent warhead
- Cys selective
- Tuning of reactivity
Examples of the Сyanoacrylamides from stock
761 compounds in stock and over 920K virtual compounds
240 compounds pre-plated Covalent Screening N-nitriles Library
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.
Download SD files
761 compounds for cherry-picking
920K compounds
Plated libraries in stock:
Examples of Cyanamides
Synthetic approaches
Two complementary synthetic strategies have enabled the development of a diverse range of cyanamide compounds. On the one hand, alkylation or acylation of building blocks with pre-installed cyanamide warhead has enabled the generation of many diverse compounds. On the other hand, direct cyanation of Enamine`s vast amine collection using a novel and convenient reagent (CBX) has provided access to structurally diverse cyanamides. Validation of various synthetic approaches, combined with access to our extensive building block stock, allowed us to create a virtual library of 920,000 cyanamide compounds. Compounds from this library can be synthesized within 3–4 weeks by our parallel chemistry department.
A Subset of Enamine REAL Compounds, Valuable Addition to The REAL/xREAL Space
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.
Key Facts
- Over 70.9B new, unique compounds that complement the REAL/xREAL Space
- Over 38B compounds compliant with Ro5, and over 33B compounds compliant with Veber's rule
- Shipping from 4 weeks
- Over 80% of compounds delivered
- All compounds undergo extensive quality control by 1H NMR and LC-MS, and purity is guaranteed to be over 90%.
Applications
- Hit finding
- SAR and hit-to-lead
- Compound library extension
Novelty
The unREAL Compounds are an innovative dataset of screening compounds that unlocks access to billions of previously unknown, unique structures. Enamine specialists continuously develop new and original building blocks, expanding access to an infinite chemical space for drug discovery. In most cases, Enamine provides the ability to supply these compounds without publishing them in their in-stock catalogs and online databases (Reaxys, SciFinder, Pubchem, etc.).
Diversity
The unREAL Space is built on 620 million Bemis-Murcko scaffolds that are unique and not present in the REAL/xREAL Space. This incredible diversity of scaffolds is made possible by utilizing over 86,700 unique building blocks assembled via 24 synthetic protocols.
Accessibility
The unREAL Space and its subsets are available upon request. Please send us an inquiry to
VHL binders and their functionalized analogs
The VHL E3 ligase, a member of the Cullin-RING E3 ubiquitin ligase family, is responsible for the ubiquitination and subsequent proteasomal degradation of specific substrates, including HIF-α. PROTACs, heterobifunctional molecules, exploit this cellular machinery by recruiting target proteins to the E3 ligase, leading to their ubiquitination and degradation. The development of effective PROTACs relies on the availability of high-affinity small-molecule ligands that can bind to E3 ligases with high specificity.
With years of experience in VHL chemistry, our team has a deep understanding of this field. Our chemists continuously innovate, designing and synthesizing novel Building Blocks and exploring creative modifications of key intermediates. Leveraging this expertise, we’ve enumerated a REAL space of over million VHL-targeted compounds, which can be rapidly synthesized within 4 weeks with an impressive 80% success rate. Also, we are offering ready-to-use VHL ligand-linkers conjugate kits – sets with well-balanced linkers and common VHL binders to support your discoveries.
Examples of in-stock VHL binders
Selected publications
-
Discovery of small molecule ligands for the von Hippel-Lindau (VHL) E3 ligase and their use as inhibitors and PROTAC degraders.
Diehl C., Ciulli A. Chem. Soc. Rev. 2022, 51, 8216. DOI: 10.1039/D2CS00387B
Includes 3 sets
Examples of Enamine Basicity-Tuning Cyclobutylamine Kits
Basic set
Catalog No.
Basic set-50
Compounds
7
Amount
50 mg
Price
Catalog No.
Basic set-100
Compounds
7
Amount
100 mg
Price
Catalog No.
Basic set-500
Compounds
7
Amount
500 mg
Price
Advanced set
Catalog No.
Advanced set-50
Compounds
7
Amount
50 mg
Price
Catalog No.
Advanced set-100
Compounds
7
Amount
100 mg
Price
Catalog No.
Advanced set-500
Compounds
7
Amount
500 mg
Price
Pro set
Catalog No.
Pro set-50
Compounds
15
Amount
50 mg
Price
Catalog No.
Pro set-100
Compounds
15
Amount
100 mg
Price
Catalog No.
Pro set-500
Compounds
15
Amount
500 mg
Price