We see a booming demand for our DEL collections (Scaffolds and building blocks) and we collaborate with many of the DEL community scientists to design and access new chemical space.
DNA-encoded chemical libraries (DEL) technology is a new screening technique used by many pharmaceutical companies to generate Hits. It is different from HTS (which is more traditional) or fragment library Lead Discovery. Conceptually, it is a numbers game, much like HTS. But on a different order of magnitude. Where HTS campaigns of millions of compounds are “the norm”, a DEL screening campaign can screen BILLIONS of compounds.
DEL include large collections of organic molecules, individually coupled to DNA fragments, serving as amplifiable identification barcodes.1,2 In principle, a core molecule, or scaffold, serves as a centerpiece. It typically has 2 to 4 exit vectors for coupling of additional handles and diverse libraries of peripheric groups (one of them is used to link to the DNA fragment). This means that around each core, small focused libraries of hundreds of compounds become available and are screened at the same time. The result is a direct read out of an early SAR (Structure-Activity Relationship), which is not possible in a standard HTS. It therefore generates hits that are already very advanced and hopefully require less follow-up chemistry for efficacy. It is still necessary to do such follow-up optimization for the ADME part though …
It is important to note that scaffold diversity is very important. The decoration of those scaffolds being often automatized, the real novelty comes from the design of the scaffolds themselves. And there, there are only very few limitations. In fact, it is amazing how diverse the transformations can be despite the presence of the DNA linker and the reactions are performed in water. This gives a lot of opportunities for the creative scaffold designer to let his/her imagination go and deliver conformationally restricted scaffolds that open new uncharted territories of chemical space.
At SpiroChem, we are a leading chemistry company with an elite team of synthetic organic and medicinal chemists. We design new mono-, bi-, tri- and quadri-functional scaffolds and building blocks on an ongoing basis with a particular attention to diversity, shape, conformational restriction, sp3-character and alignment of exit vectors. We use all the latest techniques in synthetic organic chemistry, such as photoredox catalysis, to develop new chemotypes and expand the limits of the known. A number of our scaffolds (and building blocks, see below) have already been shown to have high chemical reactivity under standard DEL conditions.
What is more, we know our chemistry, and we can support and run downstream chemistry efforts to convert your hits into leads and beyond. The increased complexity of our scaffolds (relative to the usual basic commercial scaffolds) is in no way a limitation, because we master their chemistry and we can develop exit vectors and modulate properties so that you get the full benefit of working in a novel, IP-secured chemical space.
Our Spirokits of focused analogs of standard medicinal motifs, such as analogs of morpholines, piperazines, small lipophilic amines (to name a few) allow for an efficient decoration of any scaffold and the creation of efficient libraries for ADME exploration.
Contact us to help you create a new library with unexplored chemical space.