DNA-directed Libraries

First successful screening of a multimillion membered DECL inside a living cell. A 194 million member yR-DNA-directed library screened against three pharmaceutically relevant target protein, namely p38α, ACSS2, and DOCK5 yielded chemical clusters with micro/nano molar binding affinities. To circumvent the need of highly purified active protein of interest for the screening campaign and also  more faithfully reproduce the cell environment during … Read more

In vitro selection of DNA-directed library comprising 256,000 small-molecule macrocycles with improved drug-like physical properties, enabled the isolation of novel insulin-degrading enzyme (IDE) inhibitors with IC50 as good as 40 NM. A few months after the silent shutdown of Ensemble Therapeutics, the laboratory of the founder Harvard Professor David R. Liu, reports the detailed development and synthesis of a second-generation 256,000 macrocycles … Read more

YoctoReactor technology (yR) and BTE selection allowed the identification of a specific single digit nanomolar inhibitor of p38α kinase. Vipergen applied the proprietary YoctoReactor technology (yR) to the synthesis of a three building block DNA-directed library, comprising 12.6 million compounds. Binder trap enrichment (BTE) selection, using DNA-tagged p38α kinase as target protein, enabled the straight identification of a new specific and potent small molecular inhibitor with IC50 as good as 7nM … Read more

Ensemble Therapeutics applied the principles of DNA-directed library (i.e., DNA-programmed chemistry) to the construction of a 160000 macro-cyclic peptidomimetic small molecule collection for disrupting the protein−protein interaction between the XIAP binding domains (BIR2 and BIR3) and caspase initiator to promote apoptosis. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die. The mechanism of apoptosis is … Read more

Liu et al. described a number of DNA-templated applications for the de novo discovery of bioactive molecules. Selection and decoding of a 13’824-membered macrocycle library against 36 different target proteins allowed the isolation of various new classes of kinases modulators. Selected compounds included p38α-MAPKAP2 cascade inhibitor (11μM), VEGFR2 activators (up to 300% activity enhancement at 100 μM concentration) … Read more