Speed, Quality, and Novelty
Advancements of new technologies and promising discoveries is progressing faster and more intensively with each passing day. Therefore, Enamine, a global leader in the chemical building block market, has developed a special product - the Fast MADE Building Blocks. This is a special set of Enamine MADE (MAke-on-DEmand) building blocks (BBs) that will be synthesized and delivered to our customers in ultra-short terms.
Such compounds are synthesized within 7‑10 days, through 1-3 commonly utilized procedures (Amidation, heterocyclization, arylation, Grignard reaction, reductive amidation, etc.) with a very high success rate (more than 80%). They are readily available through proven synthetic protocols using our in stock building blocks. It takes just 2‑3 weeks from the moment of the order to deliver to our customers.
Well-validated synthesis protocols and the availability of a large amount of various starting raw materials in stock (above 300,000 BBs in gram quantities and 10,000 BBs in quantities > 1 kg), allow us quickly and easily synthesize more than 90M Fast MADE Building Blocks.
Our highly qualified and experienced specialists are constantly working to ensure that the set of the Fast MADE Building Blocks continues to grow, and synthesis protocols are being improved.
The jointly acquired broad experience now allows us to offer our customers a large number of diverse compounds. Almost all the compounds are novel, and not available through other suppliers. The Fast MADE includes diverse classes of chemical compounds, such as alcohols, primary and secondary amines, amides, sulfonyl chlorides, halides, carboxylic acids, etc.
Key Facts:
- Your ordered compounds and compound sets will be synthesized and delivered to you within a period of up to 2‑3 weeks;
- In-stock availability of raw materials directly at Enamine enabling immediate start of the synthesis;
- Well-developed, standardized, and improved synthesis protocols allow us to obtain targeted Building Blocks with very high success rates (more than 80%) in the shortest possible time;
- All of our chemical building blocks undergo extensive quality control by NMR and LC-MS, and purity is guaranteed to be over 95%.
You can conveniently make an online substructure or similarity search for novel, previously unseen compounds at our partner website: https://chem-space.com/search, the only online resource that has the comprehensive and most up-to-date collection of Fast MADE Building Blocks.
Molecular Properties
Since 2018, several drugs have been recalled from the market following the discovery of N-nitrosamine impurities in their commercial batches. The N-nitrosamines have been linked to an elevated risk of several cancers especially in case of continuous intake. Since 2020, the FDA and other authorities worldwide have mandated control of N-nitrosamine levels in commercial drugs.
Mechanism
N-nitrosamines can form as impurities in the process of chemical drug production. Following the drug administration, oxidation of the N-nitrosamine species by cytochrome P450 leads to downstream production of cancerogenic diazonium salts that damage DNA by alkylation of susceptible nucleobases. Acceptable daily intake limits have been mandated by authorities for a large panel of N-nitrosamine species, which is, however, not explicit.
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We offer
More than 200 N-nitrosamines from stock on a 5-10 g scale.
Most diverse linkers for your discovery program
Bifunctional Molecules such as PROTACs, DUBTACs, LYTAC, AUTOTAC, GlueTAC, CHAMP, and others are among the hottest new modalities in modern Drug Discovery. These molecules can be considered as two actives connected with linkers. Numerous scientific studies suggest that the linker’s length, polarity, and rigidity can play a crucial role in a tertiary complex formation, its stability, and the pharmacokinetic (PK) properties of the bifunctional molecules. Quick and easy access to various linkers is essential for a rapid “Linkerology” search since it is next to impossible to predict a “perfect linker” for a given target. Vast majority of protein degraders were developed through the most empirical optimization of linker composition, often driven by the commercial availability of PEG- and carba-precursors.2 As Derek Lowe mentioned in his post on Linkerology: “The only thing we can say for sure now, is that it's a complex situation with a lot of room for surprises. Go make some more linkers!”
Being the largest supplier of Building Blocks, Enamine provides a wide assortment of linker molecules from stock. They can be used for the rapid design and synthesis of different bifunctional molecules. Fine adjustments can also be made by searching over 5 million MADE Building Block linkers.
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Linear linkers
These are classical tools that are often applied for the design and investigation of new PROTACs, DUBTAGs, and other bifunctional molecules. Enamine offers a diverse collection of building blocks for the construction of linear PEG- and carba-linkers with different lengths, tail functional groups (FGs), and composition. This collection is continuously enriched with new compounds from our synthesis program.
Examples of PROTACs with linear linkers.
Advanced linkers
More complex, with strained structure linkers have become popular in the last couple of years. These advanced linkers contain in their structure cycles, spirocycles, double and triple bonds, and multiple heteroatoms.
Based on the literature data, we singled out the following general criteria for this linkers type: 1-3 cycles, maximum one aromatic/heteroaromatic ring, presence of end functional groups (with or without protection), absence of side functional/reactive group/motifs. The corresponding linker Building Blocks are available from our stock. We can also readily synthesize any other linker molecules upon your request.
Mono-Boc diamines
Mono-Boc diamines are the most popular linkers in the design of bifunctional molecules (first of all PROTACs). Various diamine linkers can be found in the structures of the drug candidates such as ARV-110, ARV-471, CFT8634, and FHD‑609. Recently Janssen chemists have demonstrated a straightforward Direct-to-Biology (D2B) approach to new protein degrader discovery starting from diverse N-Boc diamines.1 Enamine provides an outstanding collection of diverse diamines (by flexibility/distance/shape/polarity) which are useful for linkerology studies of new bifunctional molecules.
Other linkers
Besides diamines other linkers with diverse end-functional groups are widely used in the design of bifunctional molecules. Enamine provides various linkers with different combinations of functional groups (e.g., OH/halogen-acetylenes, amino acids, aminoacetylenes, aminoazides). Upon request, we can propose a set of linker Building Blocks according to your criteria.
Selected publications
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Direct-to-Biology Accelerates PROTAC Synthesis and the Evaluation of Linker Effects on Permeability and Degradation.
ACS Med. Chem. Lett. 2022, 13, 7, 1182–1190. DOI: 10.1021/acsmedchemlett.2c00124 -
Current strategies for the design of PROTAC linkers: a critical review.
Explor. Target Antitumor Ther. 2020, 273-312. DOI: 10.37349/etat.2020.00018
Access to the diverse and highly representative Enamine building block collection provides obvious benefits for SAR exploration and other library synthesis projects. However, they are often outstripped by the costly routine in-house weighing operations and the necessity to develop and maintain an internal building block archive. With Enamine, you can purchase a pre-weighted building block set in exactly the quantity you need for your next reaction and still have full access to our entire stock collection without limitation to your selection. Please download our stock building block database from here.
The building blocks will be weighted free-of-charge in low-mg- or µmol-amounts in the containers of your choice. These can be 1 Dram or 2 Dram reaction vials with pressure relief caps, any other vials appropriately labeled with our building block ID’s or 2D-barcoded 0.75 or 1.4 mL tubes in racks. You can also provide your own reaction containers. All you need to do, when you receive the reagent set, is to add solvent and carry out a reaction with your starting compound.
Quick Building Block* / Quick Monomer Program. In case of the regular needs for supply of the building sets we offer an optimized set-up enabling minimal delivery times. It is based on the pre-agreed order and logistics workflow and flat building block prices. When all terms are part of our agreement, delivery can take as quickly as 1-3 days.
* The term “Quick Building Blocks” was coined by Christopher J. Helal, et al. ACS Medicinal Chemistry Letters 2019 10 (8), 1104-1109 in their study of a novel business partnership that aims at just-in-time, economical access to a large number of diverse commercial building blocks.
Building blocks are the essence of our business and our main advantage used to build up all other products and services. Get all the compounds you need directly from the producer in one place, and embody your creativity with our building block collection.
MADE Building Blocks
Discover unexplored unique chemotypes with our MADE collection. MAke-on-DEmand (MADE) building blocks are a 1.35B catalog of reagents that can be synthesized within several weeks using short pre-validated reaction sequences, our chemical experience, and starting materials from our stock.
Fast MADE Building Blocks
To save your time and efforts, we conveniently categorized the entire Enamine's building blocks collection by chemical functional groups: carboxylic acids, primary and secondary amines, boronic compounds, etc. Download latest selections and special subsets as separate SD files.
