The ALIDC collection consists of a carefully curated library of 200,000+ compounds suitable for lead identification via high throughput screening (HTS) or iterative screening (see Applications of the Library). The collection is designed to represent the chemical space of over 1 million diverse, lead-like, commercially available compounds from multiple reliable vendors. To derive the ALIDC collection, a structure-proprietary algorithm was built to balance overall chemical diversity with a peak nearest neighbour count of approximately 10 to maximise the chemical space sampled and the probability of identifying hit compounds. The collection has been curated within acceptable lead/drug-like space to appeal to the needs of a wide range of users. For example, molecular weight was kept in the range of 260-600, cLogP 1-6 and TPSA 60-160. A wide range of undesirable chemotypes and functional groups including compounds known to interfere with common assay readouts have also been omitted during the library selection.


Applications of the Library:


Traditional HTS using a miniaturised assay format can be carried out using the full ALIDC collection or on a smaller subset. Selection of a subset based on virtual screening or analoging from a current hit molecule is also possible. A screening set suitable for phenotypic assays can also be selected either as a general set or for target specific screening. These compounds are selected using in silico physiochemical property filters to give a high likelihood of possessing cell permeability. Smaller library sets can be tailored for the screening application and enables custom plates to be prepared cutting costs and increasing efficiency.

As an alternative to HTS, the relatively new approach of Iterative Screening may be implemented. The ALIDC library was designed to balance diversity and compound clusters with iterative screening in mind. Here, a smaller highly diverse set of compounds (typically 2,000 to 10,000 compounds) are screened, the hits are analysed, and a second sub-library is selected for further screening based on the output of the first hit set. From the ALIDC collection, diverse sub-libraries varying in size from 2,000 to 10,000 compounds have been identified for initial screening. Progressive iterations can be carried out using the data from the prior iterations using similarity searching until a satisfactory outcome is achieved. Iterative screening is less resource intensive and has been shown to deliver hits faster but still identifying the top hits found from a full HTS screen. [REF: Paricharak, Shardul, Adriaan P. IJzerman, Andreas Bender, and Florian Nigsch. “Analysis of iterative screening with stepwise compound selection based on Novartis in-house HTS data.” ACS Chemical Biology 11, no. 5 (2016): 1255-1264.].


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