Seglins: Diversity by design
Summit’s objective in developing Seglin™ technology was to build on the intrinsic activity of iminosugars and identify potent and selective drug candidates against high-value drug targets that are not addressed by conventional chemistries.
To achieve this objective, Summit has created a compact yet maximally diverse collection of Seglins that provide comprehensive coverage of natural carbohydrate space to allow rapid generation of lead candidates.
Learning from history
The development of iminosugars draws parallels with the development of anti-viral nucleosides, a class of compounds that after an unimpressive start 35 years ago eventually produced over 20 marketed drugs with annualised sales in excess of $35 billion. If a basic, diverse set of core structures had been available at an early-stage and subjected to systematic evaluation against emerging viral targets, leads into each of the marketed drugs could have been rapidly identified.
Summit believes Seglins are amenable to this type of systematic approach to allow rapid identification of new drug leads with the advantage that Seglins are expected to have wider utility in many therapeutic areas across the glycobiology spectrum and beyond.
A maximally diverse collection
The Seglin collection consists of three sections. ‘Tier 1’ comprises of a core set of structures that provide comprehensive coverage of all natural (D-) and unnatural (L-) hexose and pentose space. This ensures the Seglins collection defines all possible carbohydrate stereochemistries. These ‘Tier 1’ structures are supplemented with additional ring systems, isomeric forms and key motifs that are common in mammalian glycobiology to produce a more diverse ‘Tier 2’ set of compounds.
Screening of the ‘Tier 1’ and ‘Tier 2’ sets is routinely undertaken to allow early-stage identification of active compounds. Chemical optimisation to enhance potency and selectivity of the hits is undertaken and this process can be rapid due to any stereochemical requirements for molecular recognition already being encoded into the active structure. The optimisation process yields the largest ‘Tier 3’ set of compounds and these are further supplemented by synthesising additional analogues and derivatives using medicinal chemistry strategies. ‘Tier 3’ compounds have also provided leads in their own right in a number of programmes. It is important to note that each Seglin compound is synthesised as a single stereoisomer.
