DNA encoded library derived molecule properties and library productivity

2018-05-22T09:33:31Z (GMT) by O. Eidam
NA encoded library (DEL) screens allow for screening of millions of small molecules in a simple manner and provide novel chemical starting points in target-based hit identification. At Roche Innovation Center Basel we analyzed the physical properties, novelty, or structural diversity of 57 small molecules derived from two DNA encoded library screens run against two protein targets, employing mixtures of 16 different libraries.
In this presentation I will provide an assessment of the physical properties of 57 DEL-derived molecules from two drug target screens with an emphasis on drug-likeness, diversity and novelty, and a comparison to publicly available chemical space.
I will also highlight our observations related to the productivity of DNA encoded libraries: the total number of different small molecule structures potentially contained within each of the 16 libraries screened lies between 106 (1 million) to 1011 (100 billion) unique molecules; the median is 30 million unique molecules. We find that there is no clear relationship between the size of a library and its productivity, which we define as the number of active clusters obtained from a library (Figure 1). Empirical reasons for this finding and its implications for the design of future DNA encoded libraries will be discussed.

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CC BY 4.0