Compounds with annotated activity data
15 457 compounds
We have synthesized and collected over 15k compounds with known biological activity including over 1 123 FDA-approved drugs, tool compounds, metabolites, prodrugs, and drug candidates currently in clinical trials.
- Fully annotated: all compounds are provided with literature references and biological activity data.
- Custom Synthesis and Compound Sourcing: we can supply almost any compound either through in-house synthesis or through our supplier network.
- Analogs: provided by searches in 76.9B compounds across our Screening Collections, REAL Database and REAL Space or by enumeration of new hit follow-up libraries.
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15 457 compounds for cherry-picking
A comprehensive searchable database including literature references and activity/selectivity values towards different targets is available through a custom request form.
The World largest and continuously enhanced source of in-stock fragments
259 380 compounds
Fragment screening has become a mainstream technology in small molecules Drug Discovery programs and not only. Chemical Biology, which is extremely rapidly evolving now, needs reliable tools to navigate research. Fragments have also proved their efficacy in the discovery of new chemical probes, which reveal fundamental biological insights.
Committed to expanding chemical space Enamine has synthesized over 300 000 building blocks and developed REAL Compounds, both to contribute to the success of its abundant Fragment Collection. Not only reflect our fragments contemporary trends in FBDD, such as fragments bearing covalent warheads and photolabels, but also can they be easily grown into leads. All fragments can be easily followed with analogues from stock or through express synthesis.
We collaborate with the leading experts in FBDD to design and synthesize libraries for the most challenging projects filling gaps in the accessible chemical space. We continuously improve the quality of our fragments by providing more assurance on their solubility and stability. We keep screening our new fragments to assure stability of DMSO solutions and comply with solubility of at least 100 mM in DMSO and 1 mM in aqueous buffer.
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Key features
- Novelty and high chemotype diversity
- Replenished, significant amount in stock, typically 100 mg+ and purity 95%
- Design of custom libraries – target focused, assay-dedicated or chemotype based
- Close analogs in stock and quick follow-up library synthesis
- Hit confirmation and follow-up support
Currently, we offer 14 different pre-plated fragment libraries. We extensively work on improvement of all fragment libraries to bring the best starting points to your Fragment screening campaign.
Our presence in global FBDD
- Moonshot COVID-19 project: Fragment to lead
- Enamine to be the exclusive supplier of Astex’ MiniFrag Library. Read press release >>>
- Enamine Supplies DSI Poised Fragment and Analogue Libraries to Diamond Light Source1 XChem Facility and SGC Oxford. Read press release >>>
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Fragment libraries designed to be functionally diverse recover protein binding information more efficiently than standard structurally diverse libraries
Carbery A., Skyner R., von Delft F., Deane CM. Cold Spring Harbor Laboratory 2022. DOI: 10.1101/2022.03.18.484642 -
Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening
Resnick E., Bradley A., Gan J. et al. J. Am. Chem. Soc. 2019, 141, 22, 8951–8968. DOI: 10.1021/jacs.9b02822 -
Expanding the Repertoire of Low-Molecular-Weight Pentafluorosulfanyl-Substituted Scaffolds
Jose A., Guest D., LeGay R. et al. ChemMedChem. 2022, 17(7), e202100641. DOI: 10.1002/cmdc.202100641 -
An automatic pipeline for the design of irreversible derivatives identifies a potent SARS-CoV-2 Mpro inhibitor
Zaidman D., Gehrtz P., Filep M. et al. Cell Chem Biol. 2021, 28(12), 1795-1806. DOI: 10.1016/j.chembiol.2021.05.018 -
(Chlorosulfonyl)benzenesulfonyl Fluorides-Versatile Building Blocks for Combinatorial Chemistry: Design, Synthesis and Evaluation of a Covalent Inhibitor Library
Tolmachova K., Moroz Y., Konovets A. et al. ACS Comb. Sci. 2018, 20, 11, 672–680. DOI: 10.1021/acscombsci.8b00130 -
NMR quality control of fragment libraries for screening
Sreeramulu S., Richter C., Kuehn T. et al. J Biomol NMR. 2020, 74(10-11), 555-563. DOI: 10.1007/s10858-020-00327-9 -
Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease
Douangamath A., Fearon D., Gehrtz P. et al. Nat Commun. 2020, 11(1), 5047. DOI: 10.1038/s41467-020-18709-w
The Synthetically-Accessible Part of Chemical Space for Discovery
Enamine REAL® Compounds are the source and the extension to our in-stock Screening Collection. They are REadily AccessibLe through validated parallel synthesis protocols using our qualified in-stock building blocks, thus representing the synthetically accessible part of chemical space. Ordering the REAL Compounds is as easy as being available from stock.
Some applications of Enamine REAL include:
- Hit exploration
- Hit-to-Lead
- Compound collection enhancement
Quick facts
- Zillions of novel compounds for cherry-picking
- Synthesis within 3-4 weeks, over 80% of compounds delivered on time
- Recognized by the scientific community, over 130 publications citing Enamine REAL
Explore Enamine REAL:
- Enamine REAL Space. The most recognized and most used subset of Enamine REAL that includes the REAL Database. It can also be accessed via a convenient chemoinformatics tool, infiniSee by BioSolveIT, that generates Enamine REAL Compounds on the fly. Enamine REAL Space is also offered as an enumerated version, provided upon request.
- Enamine xREAL Space. Four! trillion molecules! This subset of Enamine REAL is available through infiniSee xREAL by BioSolveIT and as a part of Chemspace Discovery Services.
- Enamine unREAL Space. A new subset of the REAL compounds that complements the REAL and the xREAL Space. This dataset is provided upon request.
How to get started:
Online search. You can conveniently search for the REAL compounds using substructure and similarity queries on EnamineStore.com, providing access to the entire REAL Database.
Other options:
- Arthor/SmallWorld by NextMove
- Hyperspace plugin for DataWarrior by Alipheron
- ZINC22
- Ignite by Cresset
- Orion (FastROCS) by OpenEye
- KNIME via Chemspace Search Node
- Maestro Suite by Schrödinger
- PharmScreen by Pharmacelera
- RIDE by MolSoft
Novelty
Enamine REAL compounds are a next-generation screening compound dataset that allows for exploration of zillions of previously unknown structures. Enamine continuously develops new and innovative building blocks. These building blocks, while combined via well-validated synthetic procedures, provide access to new compounds to drive your projects forward. In most cases, Enamine provides an option of supplying these compounds without publishing them in our stock catalogs and sources like PubChem, Reaxys, and SciFinder.
Diversity
Enamine REAL compounds are based on millions of Murcko scaffolds. We achieved this enormous variety of scaffolds using over 200 000 building blocks assembled via 172 synthetic protocols. Diversity subsets of the REAL compounds are available here.
Drug-likeness
Billions of the REAL compounds are Ro5 and Veber's rule compliant:
- MW ≤500
- SlogP ≤ 5
- HBA ≤ 10
- HBD ≤ 5
- RotBonds ≤ 10
- TPSA ≤ 140
Please use the REAL Database (link) to access these compounds.
Prices
All Enamine REAL Compounds have flat prices. They come from two categories.
- The s-REAL compounds are synthesized via standard 1-2 step procedures with 85%+ success rate.
- The m-REAL compounds are 50% more expensive than the s-REAL compounds because their synthesis involves either multistep synthesis procedures, or use of expensive building blocks, or the products require special purification. Synthesis success rate is over 75%.
- The u-REAL compounds are synthesized via advanced 1-3 step procedures with 65%+ success rate.
Ideas for a quick start
- Diversity set. You can make a pilot screen of REAL compounds using one of the diverse subsets from REAL Database
- Download infiniSee or infiniSee xREAL and run a search within 76.9B or 4 trillion! compounds on an ordinary computer
- Online search. You can conveniently search for the REAL compounds on EnamineStore.com that provides access to the REAL Database.
Yes, Enamine REAL Compounds are not in stock, but...
- All building blocks available in OUR stock
- Each building block has already been tested to comply with the synthesis procedure
- We know in advance which of the synthesis protocols developed in-house to use
...we deliver as if the compounds were available from stock
Selected publications on the use of REAL Compounds
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Identifying Novel Inhibitors for Hepatic Organic Ani-on Transporting Polypeptides by Machine-learning based Virtual Screening.
Tuerkova A, Bongers B, Norinder U, Ungvári O, Szekely V, Tarnovskiy A, et al. ChemRxiv 2021, in press. DOI: 10.26434/chemrxiv-2021-whpsw -
Structures of the σ2 receptor enable docking for bioactive ligand discovery.
Alon, A., Lyu, J., Braz, J.M. et al. Nature 2021, 600, 759-764. DOI: 10.1038/s41586-021-04175-x -
Synthon-based ligand discovery in virtual libraries of over 11 billion compounds.
Sadybekov, A.A., Sadybekov, A.V., Liu, Y. et al. Nature 2021. DOI: 10.1038/s41586-021-04220-9 -
An open-source drug discovery platform enables ultra-large virtual screens.
Gorgulla, C., Boeszoermenyi, A., Wang, ZF. et al. Nature 2020 580, 663-668. DOI: 10.1038/s41586-020-2117-z
Practical way to start exploring REAL Database
REAL Samples
Virtual screening of the ultra-large databases can be performed iteratively, starting with a small subset. Such a diverse subset can provide essential data to teach AI-based algorithms or already result in promising hits. We have created three REAL Samples (0.1%, 1%, and 10% of the REAL Database) that allow users to explore the REAL Database depending on their computational resources. The REAL Samples have molecules that comply with the Ro5 and Veber criteria: MW ≤ 500, SlogP ≤ 5, HBA ≤ 10, HBD ≤ 5, RotBonds ≤ 10, and TPSA ≤ 140 and fully represent the REAL Database. Once hits are identified, their REAL analogs can be found at enaminestore.com
REAL Lead-like compounds
The lead-like subset of REAL Database has been obtained by filtration using the following molecular criteria: MW ≤ 460, -4 ≤ SlogP ≤ 4.2, HBA ≤ 9, HBD ≤ 5, Rings ≤ 4, RotBonds ≤ 10. Within the set, we have charted a “350/3” subset with compounds with the most stringent physicochemical profiles to have high potency for optimization: 270 ≤ MW ≤ 350, 14 ≤ HAC ≤ 26, SlogP ≤ 3, and aryl rings ≤ 2.
REAL Fragments
Enamine has a large fragment collection in stock. REAL Database expands this fragment space allowing you to find novel compounds to grow and optimize found hits. We have selected REAL fragments by applying the Ro3 criteria (MW < 300, SlogP ≤ 3, HBA ≤ 3, HBD ≤ 3, RotBonds ≤ 3, and TPSA ≤ 60) to the entire REAL collection. We have also extracted a single pharmacophore subset that complies with even more stringent molecular selection criteria: 140 ≤ MW ≤ 230, 0 ≤ SlogP ≤ 2, 10 ≤ HAC ≤ 16, RotBonds ≤ 3, and chiral centers ≤ 1.
REAL compounds by chemical classes
Prefiltering REAL Database by distinct structural motives that pop up frequently in virtual screening significantly reduces computational time. We have created a number of REAL Database subsets based on the presence of specific chemical moieties/pharmacophores in compound structures.
- REAL Amino Acids, 21.4M cpds, CXSMILES
- REAL Carboxylic Acids, MW ≤ 400, ClogP ≤ 3, 141.4M cpds, CXSMILES
- REAL Hydroxamates, 6.18M cpds, CXSMILES
- REAL Lead-like Aliphatic Carboxylic Acids, 83.7M cpds, CXSMILES
- REAL Lead-like Aliphatic Primary Amines, 109.6M cpds, CXSMILES
- REAL Lead-like Aromatic Carboxylic Acids, 40.7M cpds, CXSMILES
- REAL Lead-like Aromatic Primary Amines, 220.2M cpds, CXSMILES
- REAL Secondary Amines, 8-21 heavy atoms, 170.6M cpds, CXSMILES
- REAL Terminal Acetylenes, 327M cpds, CXSMILES
REAL Natural-like Product compounds
We have utilized the approach published by P. Ertl, et al. to predict the natural product-likeness of the REAL compounds. The REAL Natural-like Product compounds comprise drug-like molecules with positive natural product-likeness scores.
REAL PPI Modulators
Targeting protein-protein interactions (PPIs) is often utilized in modern drug discovery to find new medicines. Enamine& REAL PPI modulators comprise molecules that have common physicochemical profiles 400 ≤ MW ≤ 700, LogP ≤ 4.0, 0.35 < Fsp3 and 3 ≤ Rings ≤ 6 with the known PPI modulators and will be a valuable resource for novel structural motifs.
The full stock and virtual databases of Enamine’s compounds for the hit finding projects. Download, select, screen and follow-up.
