Ensemble's proprietary platform extends beyond the limits of traditional small molecule drug discovery, through DNA-programmed chemistry, which gives the company unmatched capabilities to successfully and reliably generate millions of synthetic macrocyclic Ensemblins™ as drug candidates.

The value of DPC lies in the ability to control chemical reactivity through programming:

  • Every chemical reactant and product is identified by a specific DNA tag
  • DNA hybridization drives chemical reactions and guarantees selectivity of reaction

Reactants (yellow, blue) are brought together by hybridization of associated DNA strands to form product (green).

DPC enables the highly specific control of chemical synthesis. Under mild aqueous reaction conditions, chemical building blocks attached to complementary DNA strands are brought together by specific DNA hybridization events. Such DPC reactions can be run sequentially to make more complex drug-like molecules, and it is possible to make tens to hundreds of thousands of compounds simultaneously in the same reaction mixture while avoiding chemical cross reactivity.

DPC is very effective at making macrocyclic Ensemblins. The ring closure reaction, which can be challenging under normal synthetic conditions due to competition from unwanted intermolecular reactions, occurs with high fidelity due to the reaction isolation provided by the DNA hybridization.

Ensemble screens its macrocyclic compounds for biological activity through a rapid, highly sensitive and efficient affinity selection process, which has allowed the Company to rapidly screen hundreds of thousands of macrocycles against many high-value targets to successfully generate leads. Ensemble has built a library of over 4.2 million macrocyclic Ensemblins, the largest such set of compounds ever assembled in the pharmaceutical industry.

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