By | 2022-07-15

During our synthetic and screening endeavors, we have developed a range of approaches to both chemical diversity and highly specialized (focused) compound selections. ChemDiv’s libraries have been extensively validated both in our in-house biological assays and in the laboratories of over 200 external partners including Pharma, Biotech, Academia and Screening Centers in the U.S., Europe, and Japan.

We offer a shelf-available set of over 1.6 M individual solid compounds,

Low molecular weight organic compounds collection is updated quarterly and reflects to novel insight into molecular, cell biology, availability of novel ligands or overall trends in disease areas and observe modern definitions of lead-like properties. We provide specialized chemical libraries focused on chemical diversity-, soluble diversity-, blood-brain permeability, rigid topology (spiro-heterocycles and macrolide analogs), Fsp3 character, medium- and large-size rings (macrocycles), and other criteria.

A custom selection of compounds that suits your specific needs could be dispatched in any custom format to you within 1-3 weeks.

Focused and targeted screening compounds libraries

To meet a wide range of research needs of small molecules screening projects, ChemDiv has a carefully designed set of diversified Targeted and Focused libraries. Focused and targeted compounds libraries cover over 20 therapeutic areas,  target families including GPCR, Ion Channels, Kinases, Proteases, Phosphotases, Nuclear receptors, different mechanism of actions, PPI modulators, various receptors ligands, epigenetic mechanisms and specific structural motives grouped in screening sets like mimetics compounds,  macrocylces, spiro compounds, indioles, cyclic compounds, fragments, covalent inhibitors, natural and natural-based small molecules.

There are assembled screening sets for agrochemical, including antifungal compounds, antiparasitic libraries. Small molecules conform to the Generally Recognized as Safe (GRAS) concepts in cosmetics and food industries.

SaRs-CoV (2) Targeted screening library Selection

Covalent  inhibitors screening libraries (design and warheads)

Our computational, structural biology, synthetic and medicinal screening team follows current trends in modern structure-based drug discovery to adds novel diverse and targeted compounds. The latter selections are aimed at tackling multiple targets, protein domains, pathways, cellular processes, etc. Representative examples of these biased Screening libraries include modulators of numerous protein-protein interactions, stem cell differentiation, apoptosis, proteasome cascade including diverse ligases, autophagy, epigenetics machinery, cell cycle including quiescent cancer cells, motor proteins, mitochondrial homeostasis and cell energetic, viral targets, bacterial genome, protein folding machinery including scaffolding proteins and chaperones and many others. Our general approach to these sets includes analysis of the available chemical and biological information, identification of key pathway nodules/targets, computational and ‘wet biology’ assessment of target draggability and potential binding domains. The resulting information is analyzed by our synthetic team to design scaffolds for novel chemical libraries production that are likely to interact with the designated targets yielding focused screening compound libraries and Libraries for Hit Identification.

Biological activity Annotated screening libraries

Diversity compounds library is the best solution for your chemical screening projects. ChemDiv’s diversity screening sets represent validated drug-like chemistry space of over 13B chemical compounds and 1.6M stock compounds collection.

Our compounds screening libraries have a perfect diversity scoring by Tanimoto similarity threshold, by bias against undesirable structural patterns. Structural enrichment is done with the focus on novel chemistry by Markush fragments. The scaffolds are prioritized by structural complexity, by 3D shape diversity and Fsp3 distribution range. All chemical compounds passed REOS and PAINS filters, have high MCE-18 score, optimized solubility, and «target diversity» approach in biological activity.

A list of diversity screening compounds libraries includes 9 compounds libraries prepared using different design approaches.

100,000 maximum diversity preplated screening compounds library represents 1.6m stock available screening compounds collection and 13B virtual space of drug-like and lead-like chemical compounds. The collection has perfect diversity scoring by Tanimoto similarity, includes concentric diversity subsets 20k-30k-50k-100k. Structural enrichment is done with the focus on novel chemistry by Markush fragments. All screening compounds passed REOS and PAINS, have high MCE-18 score optimized solubility and «target diversity» approach in biological activity. Chemical compounds from over 70 targeted and focused libraries are included. Customers can cherry-pick small molecules by plates.

Concentric screening diverse subsets with 100k 54k 30k and 20k compounds

300k Representative Screening Compounds Library selected with Bemis-Murcko Clustering Algorithm includes 200 000 unique BMS and number of 3-50 small molecules per each BMS.

3D-Pharmacophore Based Screening Diversity Library is designed taking into consideration that proteins contain binding sites different in their spatial geometry and potential hot-spots / binding points for small molecule compounds. Following the “Picklock” Concept, a library that contains a minimal number of compounds with high diversity in terms of potential pharmacophore points could be applied for any protein to obtain primary hits during HTS campaigns.
Each molecule has 3D-conformation generated in Corina Software. Three the most different 3-centered pharmacophore hypothesis have been automatically constructed per a conformation mainly focusing on HBA, HBD and HYD/LIPO/ARO points. All the generated pharmacophore hypothesis has been then clustered to obtain a pool of the most divers 3D-models. 13B small molecules have been subsequently screened in silico using this pool.  The most divers virtual compounds hits have been then selected from each pharmacophore pool. These screening compounds properly cover the operating chemical space.

Soluble Diversity Screening Library is aimed to improve biophysical properties including solubility and drug-like properties of the screening set while maintain its chemical diversity. We anticipate that this set will address the undesired „supra-molecular‟ phenomena in the in vitro/ex vivo assays associated with aggregation, precipitation or formation of colloidal systems.

‘Soluble diversity” set is designed consistent with key points, namely:

— Predicted high solubility of compounds (logSW > -2.0).
— High diversity of substances. The current set is built around 500 diverse scaffolds to yield a library of 10K compounds.
— Novelty. A special effort has been made to select compounds and scaffolds with good IP potential.
— High chemical quality. The special rules of ChemDiv‟s medchem filters ensure the high quality of selected drug-like molecules. All unwanted chemotypes or compounds bearing reactive groups were removed (e.g. Michael acceptors, redox agents, polyaromatics, epoxides, quinones, etc.).
— Good physico-chemical properties of compounds selected. A variety of criteria was considered for this library selection; among those are:

  • MW ≤ 450
  • ClogP < 5.0
  • ClogD < 5.0
  • RB < 10
  • HBA < 10
  • HBD ≤ 5
  • PSA < 100

3D diversity is pivotal because the molecular shape is a crucial factor in molecular recognition by a biomolecule. 3D-Diversity Natural-Product-Like Screening Library contains 1479 clusters based on the pharmacophore 3D-similarity metric and 738 unique heterocycles. The key concepts that the chemical library design is based on are 3D shape, pharmacophore diversity, drug-likeness, and chemical beauty. Natural products (NP) have been widely used for the treatment of diseases and illnesses since antient times. Analysis of natural products  over the past 30 years revealed that approximately 40% of the developed therapeutics drugs approved by FDA were NPs, NP derivatives, or synthetic mimetics related to NPs. With their highly and sophisticated biological and chemical diversity, NPs and their derivatives have been used to explore biologically relevant space. The significant impact of NPs on the discovery of therapeutic agents is based on their embedded biosynthetic molecular recognition.

The concept of Targeted Diversity chemical space is intended for the design of high-quality screening libraries of drug-like compounds that have been focused against various biological targets. Targeted diversity signifies the superposition of highly diverse chemical space on the assortment of divergent families or sub-families of targets and unique biomolecules. Targeted Diversity make possible the design of high-quality discovery chemical libraries of drug-like molecules, selectable focused against different biological targets. This concept also uses the superposition of a highly diverse chemical space on a representative assortment of divergent families & sub-families of targets, signaling, and transport molecules. The Targeted Diversity concept is a broadly applicable platform approach, for it can be used to design and/or select high quality screening libraries of drug-like compounds focused in individual therapeutics areas, target families, or control pathways.

A major benefit of Smart Library approach is that it represents a thoughtful and multi-purpose diversity set, incorporated it into one single compound library for different screening goals. Those goals may include: “Difficult” targets (no target/ligand structure(-s) known, study and interrogation of cellular processes (e.g. apoptosis, cell cycle, etc.); Signaling pathways (e.g. WNT, Hh, RTK, Ras, etc.) and “eclectic” biological targets, including cellular processes (e.g. apoptosis and cell cycle); Protein-protein interactions (the most «hot spots», e.g. XIAP, pGPCRs, beta-catenin, etc.); An entire selected therapeutic area that incorporates multiple biological targets;

The paradigm of “drug likeness” dramatically altered the behavior of the medicinal chemistry community for a long time. In recent years, scientists have empirically found a significant increase in key properties of drugs that have moved structures closer to the periphery or the outside of the rule-of-five “cage”. Herein, we show that for the past decade, the number of small molecules claimed in patent records by major pharmaceutical companies has dramatically decreased, which may lead to a “chemical singularity”. New screening compounds containing fragments with increased 3D complexity are generally larger, slightly more lipophilic, and more polar. A core difference between this study and recently published papers is that we consider the nature and quality of sp3-rich frameworks rather than sp3 count. We introduce the original descriptor MCE-18, which stands for Medicinal Chemistry Evolution, 2018. This measure can effectively score molecules by novelty in terms of their cumulative sp3 complexity.

The drug discovery process is long and expensive. Our aim is to shorten this process by producing high-quality, hit-like, lead-like, and drug-like screening compounds that generate valuable data from discovery screening programs.

If you have an existing therapeutic target but no chemical starting point, we can be your partner to find such a lead and accelerate drug discovery.

Chemical arrays as small as 20 and as large as 500 members can be custom-made or picked up from the existing stock reflective of the structure-based assessment of a target or pathway. Notably, all screening compounds are chosen to exhibit a range of drug-like and lead-like properties. Generally, our team requests ca. 2 weeks to generate and propose set of libraries (10-25+) addressing your biological interests. Select it immediately from existing stock of 1.6 M screening compounds.

All chemical libraries for lead discovery are regularly updated at the rate of 100K new screening compounds per year with our novel, IP-defined compounds resulting from the internal development. We are pleased to consider and adopt your custom protocols in order to make focused inhibitors set(s) that suit your specific needs. Our highly diverse molecules are produced using ‘traditional’ synthetic approaches with yields of up to 100-150 mg per compound and average purity greater than 92% as determined by both NMR and LCMS analyses. Complimentary to our proprietary chemotypes, we also offer a selection of custom building blocks.

In addition to producing libraries, we could be your partner of choice for screening. For the list of our in vitro, ex vivo and in vivo assay capabilities, please visit this Biology Services.

ChemDiv ensures resupply, resynthesis, immediate active chemical analogs selection, medchem FTE support for H2L.