Searchable Ultra-Large Chemical Spaces

Overview
Chemical Diversity of the Collection
Space Properties and Order Information
Commercial Spaces
Bespoke Spaces

Overview

Combinatorial compound spaces build on the concept of combinatorial chemistry, where in a reaction two or three reactants connect to form one joined product molecule. If every one of the generic reactants represents many compatible real-world chemicals, then the number of potential products is the number of possible combinations of all real-world reactants. Today, with the number of compatible compounds per reactant available and considerung multi-step reactions, the number of synthetically feasible products is well in the trillions. The entirety of all potential product structures is called an ultra-large combinatorial space (ULCS).

Over the course of the past few years, prominent building block vendors and chemistry service companies have applied their deep synthetic know-how to compile suitable reactions together with compatible lists of building blocks, forming spaces of which individual compounds can be synthesized with a high likelihood of success.

The challenge to search these spaces effciently using existing IT systems remained because billions or even trillions of compounds cannot sensibly be stored in traditional database systems. Thus efficient algorithmic solutions are needed to unlock the potential of ultra-large combinatorial spaces. Alipheron has developed algorithms to support efficient next-generation hit expansion and hit-to-lead optimization in these ULCSs by substructure or chemical similarity search within seconds, Hyperspace Search, and by 3D analogue search via shape and pharmacophore characteristics Pharos-3D.

Chemical Diversity of the Collection

We took a random and diverse compound sample from every one of the seven spaces in the current Alipheron collection. To soemwhat reflect the size differences between the spaces, we drew 200000 samples for the eMolecules eXplore-Synple space, 10000 samples for the moleculeOne space, 20000 for XtalPi Vast, and 100000 samples each for all remaining spaces. All compounds from these providers were merged into a file and the SkeletonSpheres descriptor was calculated. This metric best reflects chemical similarity from the perspective of a synthetic chemist. We then applied the UMAP algorithm to place these compounds on a 2-dimensional plane such that similar compounds are located close to each other. The outcome shows impressively that the seven different spaces, while overlapping in certain areas, indeed also cover very different areas of chemical space. Please note that by taking equally sized subsets, the space visualization does not necessarily give a quantitative picture of the real density of a particular space in a certain region. The second figure below illustrates the full coverage of each space separately.

Space Properties and Order Information

Once promising compounds are identified in any one of the spaces listed above and described below, you may send the compiled list of the compounds together with reaction- and reactant-identifiers, SMILES, Structure to the respective space vendor and inquire a quote for the required compounds. By default, the result files are returned in the .dwar (DataWarrior) format and already contain all required information listed above. If you prefer to work with .sdf or .csv files, .dwar files can be converted to these within DataWarrior.

For detailed ordering information, please inquire with us directly here.

Commercial Spaces

Enamine REAL Space

Enamine REAL Space contains more than 83 billion make-on-demand molecules that can be synthesized at Enamine extremely fast (3-4 weeks), with high feasibility (over 80%), and inexpensive. The REAL compounds are created by parallel chemistry through the compilation of more than 170,000 building blocks via 167 different synthesis protocols, underlying Enamine’s approach to design make-on-demand compounds to maximize synthesis success rate. For more information about the space or to order compounds refer to the space properties.

Chemspace Freedom Space

Chemspace Freedom Space is an ultra-large, synthetically accessible chemical space of 296 billion molecules designed to facilitate hit discovery workflows. To create Freedom Space, Chemspace selected building blocks from reliable vendors, prioritizing price and lead time. Using 40 chemical transformations, Chemspace designed custom SMARTS patterns to preselect building blocks for each reaction. ML-based filters refined these pools for high synthesizability, leading to synthons that were then enumerated to form Freedom Space. Such an approach ensures a synthesis success rate of over 80%. For more information about the space or to order compounds refer to the space properties with your wishlist as DataWarrior file, SD-file, or text file with SMILES-encoded structures.

eMolecules eXplore-Synple

The eXplore-Synple Space is the updated and combined space of two previously independent spaces, the previous eXplore space from eMolecules and the Synple space from Synple Chem. This new combined space contains about 67.4 trillion accessible molecules built from commercially available building blocks using synthetically well proven reactions. For more information about the space or to order compounds refer to the space properties.

PharmaBlock Sky Space

PharmaBlock Sciences and Alipheron joined forces in creating the PharmaBlock Sky Space, an ultra-large combinatorial space of 58 billion novel compounds, which are readily available for purchase. The PharmaBlock Sky Space is built from frequent organic reactions applied to PharmaBlock's unique and diverse building blocks, which results in a highly diverse and drug-like universe of molecules. For more information and how to order compounds refer to the space properties.

WuXi AppTec GalaXi Space

LabNetwork is proud to offer WuXi AppTec virtual library. Drawn from more than 20 years of library design and synthesis expertise and a generously stocked collection of building blocks, scaffolds and templates, the WuXi virtual library contains more than 28.6 billions compounds and has been constructed to meet the need for an expanded global set of lead- and drug-like molecules.The virtual library was created using more than 30 different reaction types, the appropriate medicinal chemistry physicochemical parameters, coupled with commercial & novel scaffold & building blocks from WuXi and the entire LabNetwork supplier set. For more information and how to order compounds refer to the space properties.

Life Chemicals LifeCheMyriads Space

Expertly designed to accelerate hit discovery and lead expansion, our bright LifeCheMyriads Space covers over 50 billion unique virtual compounds that can be synthesized on demand. Built using more than 190 in-house validated chemical reactions and a selection of proprietary and commercially available building blocks, it is confirmed to provide high synthetic feasibility and strong medicinal chemistry relevance. Being continuously expanded and supported by our reputable CRO teams, LifeCheMyriads Space is distinguished by its strong focus on structural diversity and drug-like properties. All compounds offered are synthesizable within the shortest lead-time framework, with full scientific support provided throughout early drug discovery. For more information and how to order compounds refer to the space properties.

Molecule.One D2B-SpaceM1

Molecule.One D2B-SpaceM1 is a custom, assay-ready libraries synthesized directly on plates. It is the largest direct-to-biology chemical space, comprising in total 1.5 billion compounds, designed with generative models trained on our proprietary high-throughput experimentation (HTE) data—going beyond known chemistry. D2B-SpaceM1 delivers highly diverse one-step direct-to-biology custom libraries of ~1,000–5,000 compounds for rapid hit ID and hit exploration. Compounds are delivered on 384-well plates in DMSO (1–10 mM) in an assay-ready format. Price per compound starts from $30 and analogs are available from $8–10 per well. The synthesis of up to 13,000 compounds can be completed in one week upon building-block delivery. Re-synthesis and purification of 1% of the D2B space is included in the price upon hit identification. Each compound can also be supplied in purified micro- or milligram scale upon independent request. For more information and how to order compounds refer to the space properties.

XtalPi VAST

VAST is XtalPi's actionable, billion-sized chemical space with 80%+ delivery success rate, competitive price, and unprecedented delivery time (2-3 weeks). Compounds are delivered via automation-enabled chemistry using in-stock and novel building blocks. For more information and how to order compounds refer to the space properties.

Otava ChemInfinita™

ChemInfinita is a steadily expanding make-on-demand virtual space built from commercial and proprietary building blocks and lab-validated reaction templates, designed to prioritize robust synthetic feasibility at scale. A defining feature of the collection is its deliberate emphasis on beyond- Rule-of-5 (bRo5) structures—an area increasingly important for modern drug discovery because bRo5 modalities (e.g., macrocycles and other larger, conformationally flexible chemotypes) can better engage “difficult” targets such as shallow or extended binding sites and protein–protein interaction interfaces, where conventional Ro5-biased small molecules often struggle. For more information and how to order compounds refer to the space properties.

Bespoke Spaces

We can support you in the construction of your custom space using your proprietary reactions and building blocks to be searched in 2D using Hyperspace Search or in 3D using Pharos-3D. Alternatively, you can license our Space Builder to create at your will. The spaces can be hosted on Alipheron servers or on your own infrasructure. This service also extends to technologies such DNA-Encoded Libraries (DELs). To discuss your detailed requirements, contact us using the contact form.