Ultra-Large Combinatorial Libraries

Overview
Alipheron ULCL Collection
Summary & Ordering Information
Creation of Custom Libraries

Overview

Combinatorial compound spaces build on the concept of combinatorial chemistry, where in a reaction two or three reactant molecules 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. With hundreds or thousands of compatible compounds per reactant the number of possible products may be in the millions, billions, or even trillions, if multiple reactions are considered. The entirety of all potential product structures is called an ultra-large combinatorial space (ULCL).

Over the course of the past few years, prominent building block providers 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 set free the potential of ultra-large combinatorial libraries. Alipheron has developed algorithms to search these spaces by substructure or chemical similarity within seconds, Hyperspace.

For next-generation hit expansion and hit-to-lead optimization in these ULCLs, we offer our latest invention, Pharos-3D. It identifies those molecules that possess a similar shape and at the same time similar pharmacophore features to a given 3-dimensional query molecule.

Alipheron ULCL Collection

We provide searchable access using our search tools, Hyperspace and Pharos-3D to examine and explore a contiously growing collection of ultra-large combinatorial libraries from well-trusted and globally operating chemicals providers.

Enamine REAL Space

Enamine REAL Space 2025 contains above 76 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. To order compounds of the Enamine REAL Space contact libraries@enamine.net. More information about Enamine REAL Space.

Chemspace Freedom Space

Freedom Space 4.0 is an ultra-large, synthetically accessible chemical space of 142 billion molecules designed to facilitate hit discovery workflows. To create Freedom Space 4.0, Chemspace selected building blocks from reliable suppliers, 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 4.0. Such an approach ensures a synthesis success rate of over 80%. To order compounds of the Freedom Space contact sales@chem-space.com with your wishlist as DataWarrior file, SD-file, or text file with SMILES-encoded structures. More information about Freedom Space.

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 5.3 trillion accessible molecules built from commercially available building blocks using synthetically well proven reactions. For more information about the space or to order compounds of the eXplore-Synple Space contact order@synplechem.com. For more information, see eMolecules.

PharmaBlock Sky Space

PharmaBlock Sciences and Alipheron AG joined forces in creating the PharmaBlock Sky Space, an ultra-large combinatorial library 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. To order compounds from the PharmaBlock Sky Space visit the PharmaBlock’s product website or contact ulvs@pharmablock.com. More information about PharmaBlock.

Life Chemicals Space

More information coming soon.

WuXi AppTec Space

More information coming soon.

Summary & Ordering Information

Once you have found promising compounds in one of our partner’s commercial spaces, you may send a list of their structures together with reaction- and reactant-identifiers to the corresponding e-mail address listed below and inquire a price quote for their synthesis.

Creation of Custom Libraries

We can support you in the construction of your custom library using your proprietary reactions and building blocks to be searched in 2D using Hyperspace or in 3D using Pharos-3D. The library 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, reach out to us at contact@alipheron.com.