Edelris, escaping flatland since 2005, illustrated by success stories

At the end of the previous millennium, it was recognized by MedChem and HTS practitioners that screening collections were severely hampered by the high content of apolar and poorly soluble molecules (high cLogP), due to aromaticity combined with a low number of heteroatoms. The era of the statistical Lipinski Ro5 (Rule of Five, and further refinements) towards orally active molecules was declared open!

Yet, vast areas of the chemical space, containing synthetically accessible and bio-relevant molecules, were still remaining unchartered. Edelris recognized, very early on, the potential of exploring these novel chemical territories. We then defined rules for increasing the accuracy to navigate efficiently these spaces and pioneered the design of synthetic compounds of affordable complexity, mimics of Natural Products, and enriched in sp3 centers (Ganesan & Ortholand).

Applying this strategy since 2005, Edelris explored relentlessly new areas of the chemical space, defining an accessible Keymical Space?, instrumental to fragment-based screening (FBS), high-throughput screening (HTS), Affinity Selection-Mass Spectrometry (AS-MS), DNA-encoded library technologies (DELT) and virtual screening (VS).

Unique topologies were designed and produced in Edelris’ laboratories from commercially available starting material, in 3-5 robust steps and fully characterized relative configuration.

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Lovering and colleagues at Wyeth confirmed in 2009, the added value of “Escaping from Flatland”, by increasing the Fsp3 (Carbon-sp3/Total Carbon Count) in screening compounds, in order to find new bio-relevant chemical matter and improve the probability of clinical successes.

Following this trend in early drug discovery, efforts were then amplified in many discovery organizations, including powerful endeavors, such as the European Lead Factory consortium, to whom Edelris strongly contributed (40,000 sp3-enriched screening compounds produced), aside from European Academic and Chem-SME partners.

For Edelris’ clients, this led to many success stories directly arising from the sp3-enriched Keymical Space?, using complementary hit-generation modalities (selection of examples below. Additional ones unpublished, for antivirals for RSV, for novel E3-ligase ligands, for GPCR or enzyme ligands, and others).

?Edelris was the pioneer and continues to be leading the discovery of sp3-enriched unique, patentable, and accessible hit compounds, which can be seamlessly derived in hit-to-lead programs in order to accelerate pre-clinical research. Edelris libraries have been found particularly successful in the case of difficult-to-drug targets. The Keymical Collections? continues to be enriched on a yearly basis, following new trends in early drug discovery, and the Keymical Covalent Collections?, containing 10 different warheads, has proven to be highly attractive.

If you want to evaluate Edelris’ innovative collections, whether covalent or not, available for cherry-picking, feel free to request an SDfile: [email protected].