Products and ServicesFragment Libraries

Fragment Libraries

The fragment-based approach to drug discovery (FBDD) has been established as an efficient tool in the search for new drugs. It has emerged as an alternative approach to traditional lead identification via high-throughput screening (HTS). Unlike HTS, FBDD identifies smaller compounds, the "fragments", which bind to different parts of a biological target. FBDD has several advantages over HTS. A primary rationale for screening fragments is that they access a broad chemical space while screening a limited number of compounds. FBDD gives a better chance for the final lead compound to have common drug-likeness parameters. Moreover, the chance of screening a compound that is a perfect match for the intended target binding site is remotely small, because so many interactions between the ligand and spatial structure of residues in active site are often involved. On the other hand there are simpler molecules (fragments) with fewer necessary interactions and thus a much better chance of orienting with the target in a favorable manner.

Life Chemicals Fragment Library with variable parameters encompasses over 68,000 screening compounds including 38,000 stock collection and 30,000 compounds from tangible databases.

To meet FBDD purposes in correspondence with the most promising trends in this field Life Chemicals has designed a number of unique Fragment Libraries:

Advanced set of Tangible Fragments (Dedicated design of compound Library for FBDD)

Life Chemicals proposes the database of 5,200 synthetically feasible compounds, which is specially designed for fragment-based drug discovery. The database is generated by virtual coupling of carefully selected set of building blocks, which define the following features of the resulting library:

  • Cornerstone of the design is high quality of the fragments which is defined by rigorous control of Phys-Chem properties

Ro3 extension, PAINS and a number of in-house developed structural filters applied;

  • High fraction of sp3-carbons in the compounds

Average Fsp3 is kept above 0.6, whereas most commercial libraries have average Fsp3 0.3–0.4;

  • Diversity of the library is controlled by a number of methods

Linear fingerprint, pharmacophore and 3D analysis

  • High novelty of the chemical structures is ensured by selection of reaction partners

Diversity analysis to eMolecules and most common vendors databases

  • Rapid SAR generation potential

Short term molecules selection and synthesis for follow-up testing analogues

Currently, synthesis of the fragment library is in progress. Over 1000 compounds have been already synthesized in 100mg+ scale.


General Fragment Library

Life Chemicals presents General Fragments Library that comprises over 38,000 small molecules with low cLogP (MW ≤ 300 Da; cLogP ≤ 3). 

To perfectly fit the FBDD purposes Advanced subset of 9,400 fragments was designed with use of expanded "Rule of Three" criteria listed below. Additionally the compounds were passed through PAINS filter.


  • MW 100 - 300
  • ClogP –2 - 3
  • TPSA < 100 Å2
  • HAcceptors ≤ 4
  • HDonors ≤ 3
  • Rotatable Bonds ≤ 3
  • LogS ≥ –3.5
  • Rings count 1 – 4
  • –NO2 group and Br count ≤ 1
  • S, Cl count ≤ 2
  • –CN group count ≤ 1
  • Benzene count ≤ 1


Life Chemicals Fragments collection is available for cherry-picking and selection of custom diversity sets. You are welcome to download the databases in db or sd format.


Superior Fragment Library

The process of synthesis of the Fragments is guided by a heuristic rule, called Rule of 3, implying the compounds to have lower molecular weight and lower molecular complexity than suggested by Lipinski's Rule of 5. Advanced tuning of "Rule of 3" parameters gives the Fragments being perfect elements for generation of leads with excellent ADME profile.

Life Chemicals Superior Fragments Library was designed by applying ultimately rigorous selection criteria to the Life Chemicals stock screening compounds collection: "Rule of three" and TPSA ≤ 80Å2 cut. It is known that more than 80% of the drugs on the market have an estimated logSw value greater than -4. Thus the solubility filtering was also used to design Superior Fragments subset. Finally the PAINS and in-house developed toxicophore & undesired functionalities filtering parameters were applied to the selected set of compounds. Physicochemical criteria used for the selection are as follows:

  • MW 150 – 300
  • cLogP –2 – 3
  • TPSA ≤ 80 Å2
  • H-acceptors ≤ 3
  • H-donors ≤ 3
  • Rotatable Bonds ≤ 3
  • clogSw > –3
  • Halogens (except F) ≤ 1
  • S atoms ≤ 1
  • Ring count 1 – 3
  • Fused rings ≤ 2
  • Benzene count ≤ 1


Life Chemicals Superior Fragments collection includes more than 4,200 compounds. Please download the database here.


Low MW Fragment Library

Recent tendencies in drug discovery shift towards aiming at leads with lower molecular weight and hydrophilicity. In particular, lowering upper molecular weight cut-off value (to 200–240 instead of 300) is considered by many companies practicing FBDD.

To fulfill these criteria Life Chemicals has designed Low MW Fragment Library by applying a number of physico-chemical filters its General fragments collection. The selected compounds were also passed through MedChem and PAINS structural filters. This resulted in a library of more than 3,000 compounds. Although molecular weight is the main parameter which was controlled strictly, other physico-chemical characteristics were also controlled (e. g., more than 80% of the library has cLogP<2). Advanced set of nearly 1,500 fragments was also generated by applying more rigorous physico-chemical and structural cut-offs. The datafiles can be downloaded here.

Fluorine Fragment Library

Recently it was demonstrated (John B. Jordan et al, J. Med. Chem. 2012, 55, 678-687) that the 19F NMR-based fragment screening can be used as a very efficient tool for rapid and sensitive detection of fragment hits. It was shown that although the fraction of chemical space covered by fluorine containing fragments may be limited compared to nonfluorinated fragments, similar hit rates are obtained using both methods. At the same time fragment screening with a simple one-dimensional 19F NMR experiment (with 1H decoupling) is significantly faster and, in many ways, more robust than traditional 1H-based NMR screening. The authors' method focuses on the use of the fluorine nucleus as a detection tool, and subsequent to a 19F fragment screen, protonated analogues of hit compounds can be mined and pursued in initial hit expansion. This approach can significantly add to the chemical space explored and can provide valuable information and early stage SAR to chemists.

Life Chemicals' Fluorinated Fragments Library extracted from General Fagments stock collection comprises over 3,300 fluorine-containing compounds including Advanced subset of nearly 2,000 compounds selected by following criteria:

  • only one F or -CF3 group
  • MW < 300
  • ClogP ≤ 3
  • Hb Acceptor 1 – 3
  • Hb Donor ≤ 3
  • RotBonds ≤ 5
  • Ring count 1 – 3
  • Br count ≤ 1
  • Cyano and Sulfonyl group ≤ 1
  • -NO2 group ≤ 1
  • S and Cl count ≤ 2
  • Acid group count ≤ 1
  • Base group count ≤ 2
  • No metal or reactive compounds, no undesired chemotypes, PAINS filter is applied


Please follow to download the library datafiles.


Fluorine Fragment Cocktails

Fragment screening performed with 19F NMR spectroscopy is becoming an essential and widespread method in drug discovery projects. This highly sensitive approach can be efficiently applied in laboratories with limited NMR setup. Additionally, the efficacy of fragment screening can be increased substantially by pooling or cocktailing the compounds in the library. Identification of the bound fragment at the end of the NMR experiments then becomes a case of determining the best fragment-fit.

Life Chemicals has designed unique Library of Fluorine Fragment Cocktails employing Rule of Three criteria and MedChem structure filters including PAINS. The choice of fluorinated motifs present in the library is fundamental in order to ensure a large coverage of chemical space and local environment of fluorine. The Library is pooled in a sets of 10 fragments with most different 19F chemical shifts to facilitate interpretation of the screening results. Carefully collected 100+ cocktails comprise drug-like fluorine containing fragments satisfying following parameters:

  • Mostly only 1 peak in 19F NMR spectrum
  • Purity 95%+
  • DMSO soluble at 200 mM

PhysChem Parameters:

  • 130 < MW < 300
  • -1.7 < ClogP < 3.0
  • H-bond Donors ≤ 3
  • H-bond Acceptors ≤ 4
  • TPSA ≤ 110 Å2


Structure Filters applied:

  • no reactive functional groups
  • Lilly MedChem rules
  • Ring count: 1–3


To download the full record of available cocktails in form of sdf and xls files please follow.


Bromine-Based Fragment Library

Crystallographic Fragment‐based Drug Discovery is gaining high importance in modern pharmaceutical technology. Fragments however are weak binders with partial occupancy resulting in weak, difficult-to-fit electron density. The use of brominated fragments can address this challenge, as bromine can be located uniquely via anomalous scattering, and thus, provide further insight into the nature of the target surface pocket.

Life Chemicals Brominated Fragment Library consists of over 1,300 compounds with MW ≤ 350 and cLogP ≤ 3.5. All the fragments contain only one Br-atom. Other important parameters (such as HBA, HBD, Fsp3, RotB, TPSA) are included into the data file and can be used for selection with multiple restrictions. This library is available for cherry picking, or diversity set can be arranged in accordance with customer needs.

Advanced subset of more than 800 compounds is also available selected by the following criteria:

  • No reactive compounds, no undesired chemotypes, PAINS filters applied
  • cLogP < 3.5
  • Molecular weight < 350 Da
  • H-bond acceptors = 0−4
  • H-bond donors = 0−3
  • Rotatable bonds ≤ 4
  • Number of rings = 1−3


You are welcome to download the database.


Fsp3-enriched Fragment Library

According to new trends in drug discovery involving comprehensive structural analysis of approved drugs and determination of relationships between molecular complexity and pharmacological promiscuity of drug-like compounds, Life Chemicals has extrapolated the results of mentioned investigations to Fragment library.

Recently it was revealed that the mean Fsp3 (Fsp3 = number of sp3 hybridized carbons / total carbon count) increases from 0.36 for 2.2 million molecules in discovery to 0.47 for 1,179 approved drugs. Applying of mentioned Fsp3 cut to Life Chemicals' General Frament Library resulted in Fsp3-enriched Fragment Library of more than 11,500 compounds with inherent high selectivity towards pharmacological targets.
Superposition of selection of the compounds with relatively high Fsp3 value and filtering by strict "Rule of three" criteria along with TPSA 90 Å2 cut gives rise to Advanced Fsp3-enriched Fragments subset comprising over 3,200 compounds. To ensure removal of ugly compounds the PAINS and in-house developed toxicophore & undesired functionalities filtering were also applied.
The physico-chemical parameters of Advanced Fsp3-enriched fragments are summarized in the table below.


Parameter Range Average Value
Molecular Weight ≤ 300 Da 224 Da
Fsp3 > 0,45 0,65
cLogP < 3 0,96
TPSA < 90Å2 52 Å2
H-acceptors ≤ 3 2,2
H-donors ≤ 3 1,3
Rotatable Bonds ≤ 3 2,2
Number of Carbonaromatics ≤ 1 0,5

  You can download the databases here.


Covalent Fragment Library

According to growing interest and widespread use of Fragment-Based Drug Discovery (FBDD) Life Chemicals designed the Library of Covalent Fragments based on compounds from Stock Collection. The design of selective covalent inhibitors is conceptually very attractive but in practice hard to achieve. That is because it is difficult to strike the right balance between reactivity and selectivity. Initially, Life Chemicals Stock Collection was filtered according to “Rule of three” criteria. Thereafter preliminary set of covalent fragments was created by selecting compounds with specific structural fragments (functional groups) that are known to form covalent bonds with amino acid residues in binding sites of target proteins: Lys, Cys, Ser, Asp, Glu, His and Tyr. Finally, molecules with high reactive electrophilic and nucleophilic groups as well as compounds with non drug-like core were removed using selected unwanted core fragments and selected PAINS filters.

Over 1,300 fragments were extracted. To download the database please follow.


PPI Fragment Library

Life Chemicals team has analysed literature data to prepare a set of descriptors and ranking mechanism of fragment selection. Below is a short description of identified parameters for determination of PPI-fragment likeness:

Molecular Weight150-450
Fsp3≥ 0,4
cLogP2,5 - 4,5
TPSA< 75Å2
H-acceptors≤ 5
H-donors≤ 3
Rotatable Bonds0 - 8
Hydrophobic cores1 - 6
Ring Count>0


It was shown that PPI inhibitors are typically larger and more lipophilic than inhibitors of more standard binding sites of most proteins. In this connection PPI fragments have TPSA values higher than it was claimed in a common trend of fragment-based drug design. The same applies to molecular weight of compounds, which should be between 250 and 450 Da. Thus such compounds cannot fit a standard “Rule of three” usually used for selection of fragments. It was found that small molecules targeting PPI have highly hydrophobic core within peripheral lipophilic substituents. So we propose reasonably selected hydrophobic and more spatial structures (sp3-enriched) to enhance selectivity. One more feature that characterizes PPI fragments are principal moments of inertia (PMI). For the fragments to be more three-dimensional, an additional filter was applied on the so-called flat distance in PMI plot: npr1 + npr2 > 1.1. Finally, the compounds were passed through PAINS and in-house developed undesired functionality structural filters.

The main result of compilation of the features mentioned above is a special chemical space for compounds with a common function of PPI interaction inhibition. Mean values of npr1 = 0.28, npr2 = 0.88 for the coordinates in PMI plot show the distribution of compounds in 3D space and demonstrate 3D-shape diversity.

About 2,500 compounds were extracted into Life Chemicals’ PPI Fragment Library. To get more information and download the library datafile please follow.


Fragment Library with Experimental Solubility Data 

This library consists of low molecular fragments with experimentally measured solubility in DMSO and phosphate buffer solution at pH7.5. Designed according to industry standards this library provides you with good quality hits for your fragment screening programs.

Life Chemicals’ Fragment Library with Experimental Solubility Data includes more than 12’800 compounds mainly from our Advanced Set of General Fragment Library, with confirmed experimental solubility at 200 mM in DMSO, and available data at the above-mentioned concentrations in phosphate buffer. 81% of the library are soluble in buffer at 1 mM, and 66% – at 5 mM. Most of the compounds were passed through our internally developed MedChem structural filters. For more than a half of the library, physico-chemical parameters correspond to the criteria used to design Life Chemicals’ Advanced Fragments Set listed in the table below:

Parameter Range
MW 100 … 300
ClogP  –2 … 3
TPSA  < 100 Å2
HAcceptors  ≤ 4
HDonors  ≤ 3
Rotatable Bonds  ≤ 3


Please follow to download the database.


3D Fragments Library

Although most fragment libraries are diverse, having been selected to contain a good balance of properties, they all tend to have limited shape diversity. In this context has been established that higher three-dimensionality (3D) of molecules is a desirable feature of drug candidates and is correlated with successful passage of molecules at the various stages of clinical development. The use of more complex and sp3-rich (more 3D-like) fragments would certainly increase the drug-like fragment chemical space, which might in turn be advantageous in exploring more demanding biological targets.

Life Chemicals has designed drugable 3D fragment library using the appropriative set of physicochemical properties and descriptors that allow to evaluate 3D-dimensionality and diversity of the molecules. Principal moments of inertia (PMI) was used as a efficient method to calculate and evaluate the 3D-dimensionality and diversity. Fraction of sp3-carbons and chiral atom count in the molecule also proved to be essential descriptors for successful 3D library design.  

The following basic criteria were used to improve 3D shape functionality of our fragment library: 

  • 100 < MW < 300
  • ClogP ≤ 3
  • HBD ≤ 3
  • HBA ≤ 4
  • RtB ≤ 3
  • Fsp3 > 0.47
  • TPSA ≤ 100Å2
  • Ring count: 1 – 4
  • at least 1 chiral center
  • no more than 1 -cyano, -nitro or bromine group
  • no more than 2 S, Cl atoms
  • undesired functionalities were removed (PAINS and in-house developed filters)
  • checking for the sufficient novelty
  • ideally 2 points of functionalization


Totally more than 1,500 fragments were selected. You are welcome to download the database here.


Natural Product Like Fragment Library

Life Chemicals presents a collection of Natural Product-like fragments, which was generated via Scaffold Tree approach. More than 17,000 level-two and level-three scaffolds were extracted from Universal Natural Product Database (comprising more than 220,000 structures in its current version) using scaffold tree analysis. After removal of ugly and primitive chemotypes, the remaining ca. 4,000 structures were used for substructure search in Life Chemicals fragment collection. In addition to that, fragments derived from scaffolds showing at least 85% similarity to the natural product-derived scaffold set mentioned above were also selected. The combined database was subjected to additional structural filtering to give more than 3,200 Natural Product-like fragments.

To download the Library datafile please follow.

"Start Small & Stay Small" Zenobia Therapeutics and Life Chemicals joint fragment library

Life Chemicals and Zenobia Therapeutics have teamed up to offer a comprehensive Low Molecular Weight Fragment Screening Library "Start Small & Stay Small" developed by scientists of both companies.

Zen-Life Fragment Library properties:

  • 500 compounds diverse fragment library hand-picked up to cover chemical space
  • Composed of scaffold types commonly found in drugs and related analogues
  • Designed to facilitate rapid medicinal chemistry optimization
  • Hand picked up for maximum core diversity and balanced functionality
  • Known problem and non-drug-like compounds (e.g. reactive, unstable in vivo) removed


Please see additional information about the library in this flyer. All compounds are available for immediate delivery from stock.