The industry-leading library for fragment-based drug screening
Fragment screening has become a method of choice in the quest for rapid identification of new lead molecules in small-molecule drug discovery. Compared to traditional compound screening, it offers a higher hit probability and fewer fragments that need to be screened. The process is like assembling building blocks into a key that fits into a lock.
We have selected 2,500 high-quality chemical fragments from our collection of more than 30,000 to comprise the Thermo Scientific Maybridge fragment library—a proven, industry-leading library due to its diversity, pharmacophoric content, and novelty.
Available Maybridge fragment library formats for small-molecule screening
For libraries containing fluorine, bromine, or pre-fragments, see Specialty fragment libraries below.
Maybridge fragment library formats
| Format | Recommended usage |
| Entire library (2,500 compounds) | Highly recommended. Provides the highest hit probability. |
Core library set (1,500 compounds) |
Encompasses the diversity of the entire library. Suitable for rapid and exploratory work. |
| Supplement library set (remaining 1,000 compounds) | For those who have screened the core set, provides an additional opportunity to identify more hits. |
| Customized set | Your own selection of any number of fragments. Our searchable database allows rapid selection of fragments based on substructure and calculated Ro3 parameters. |
For complete convenience, all libraries are custom weighed to your requirements in milligram or micromolar quantities. They may be ordered neat or in DMSO or D6DMSO, in plates or vials.
Specialty fragment libraries for small-molecule screening
Fluorine is frequently substituted in drug molecules to help modulate potency and improve physiochemical and pharmacokinetic properties of compounds, with about 20% of known drug molecules containing a fluorine atom. In fragment screening, fluorine labels offer advantages for biophysical screening using NMR as well as crystallography, enabling unambiguous orientation of fragments in observed electron density. We offer a complete Maybridge fluorine compound collection and a novel fluorine-labeled fragment library, as well as libraries of bromine-labeled fragments and “pre-fragments.”
Maybridge specialty fragment libraries
| Library | Number of fragments | Description |
| Maybridge fluoro-fragment collection | >5,300 | Complete set of fluorine-containing fragments ideal for 19F NMR-based fragment screening. |
| Maybridge 19F fragment library | 380 | This diverse subset of the Maybridge fluoro-fragment collection, with 19F NMR spectra available for every compound, is demonstrated to have appropriate properties for fragment screening using biophysical methods. Developed in collaboration with Argenta and the University of Kent. |
| Maybridge bromo-fragment collection | >1,500 | Bromine-containing fragments for X-ray-based fragment screening. |
| Maybridge pre-fragment collection | >3000 | A valuable source of reactive “pre-fragments”—building blocks for synthesizing your own fragments or evolving your hits. |
Complex sample NMR spectrum vs far simpler 19F fluorine-labeled NMR spectrum. (left) NMR spectrum for the fragment (1-Methyl-1H-imidazol-4-yl) methylamine (CC03613) in PBS with the chemically encoded shift data of all compounds in the fragment library. 1H-NMR spectra in aqueous conditions with full structural information are available on request to accelerate your screening workflow by avoiding having to run an 1H-NMR baseline. (right) 19F NMR spectrum for 1-Methyl-5-(trifluoromethyl)-2,3-dihydro-1Hbenzo[d]imidazole-2-thione (TG00013). The far simpler 19F NMR spectrum simplifies interpretation, facilitating the use of “cocktailing” and allowing multiple compounds to be screened together.
Properties of the Maybridge fragment collection
In fragment-based drug screening, the Rule of 3 (Ro3) is equivalent to Lipinski’s Rule of 5 for compound screening.1 The Ro3 proposes that molecular weight should be <300 Da, the calculated partition coefficient (cLogP) should be £3, and the number of hydrogen bond donors and acceptors should each be £3. In addition to Ro3 criteria, the Maybridge fragment collection has been filtered for purity and potential “false leads” to allow you complete freedom to design a library that meets your specific needs.
Properties of the Maybridge fragment collection
| Attribute | Implications for the Maybridge fragment collection |
| Rule of Three (Ro3) compliance | Delivers superior absorption, distribution, metabolism, and excretion (ADME) attributes |
| Exceptional diversity | Tanimoto similarity index = 0.66 based on standard Daylight fingerprinting |
| PAINS-free | Filtered to remove pan-assay interference compounds (PAINS), which react nonspecifically with numerous biological targets rather than specifically with one |
| Experimentally measured solubility | Designed for solubility of fragments in PBS buffer (1 mM), ensuring robust screening data and minimizing candidate attrition |
| Assured quality of >95% | Nuclear magnetic resonance (NMR) spectrum is available for each of the 2,500 compounds in both DMSO and aqueous conditions |
| Optimized via SPR | In collaboration with GE Healthcare, a clean surface plasmon resonance (SPR) screen was run on a Biacore system to remove promiscuous binders |
| Chemically “clean” | Filtered to remove toxic and reactive groups |
| Pharmacophore-rich | But not too complex to allow simpler interpretation of results |
| Fragment hopping | The “fragment hopping” approach to drug design is facilitated across the entire Maybridge portfolio for effective pharmacophore investigation |
1Jhoti H, Williams G, Rees DC, Murray CW. The ‘rule of three’ for fragment-based drug discovery: Where are we now? Nat Rev Drug Discov. 2013; 12: 644. PubMed
Examples of Maybridge fragments
Success stories for Maybridge fragment libraries
The Maybridge Fragment Library has been the source of many successful fragment screening projects including pyrozinamide, profiled below.
Negatu DA, Liu JJJ, Zimmerman M, et al. Whole-cell screen of fragment library identifies gut microbiota metabolite indole propionic acid as antitubercular. Antimicrob Agents Chemother. 2018; 62: e01571-17. PubMed
Tuberculosis (TB) remains a global health threat, killing 1.34 million people in 2016. The high prevalence of drug-resistant Mycobacterium tuberculosis strains is a medical urgency and calls for the development of new drugs active against TB.
Several key antituberculosis drugs, including pyrazinamide, with a molecular mass of 123.1 g/mol, are smaller than the usual drug-like molecules. Current drug discovery efforts focus on the screening of larger compounds with molecular masses centered around 400 to 500 g/mol. Fragment (molecular mass <300 g/mol) libraries have not been systematically explored for antitubercular activity. Here we screened a collection of 1,000 fragments, present in the Maybridge Ro3 library, for whole-cell activity against Mycobacterium tuberculosis.
Twenty-nine primary hits showed dose-dependent growth inhibition equal to or better than that of pyrazinamide. The most potent hit, indole propionic acid [IPA; 3-(1H-indol-3-yl)propanoic acid], a metabolite produced by the gut microbiota, was profiled in vivo. The molecule was well tolerated in mice and showed adequate pharmacokinetic properties. In a mouse model of acute M. tuberculosis infection, IPA reduced the bacterial load in the spleen 7-fold. Our results suggest that IPA should be evaluated as an add-on to current regimens and that fragment libraries should be further explored to identify antimycobacterial lead candidates.
For Research Use Only. Not for use in diagnostic procedures.