In 2004, NIH founded the Molecular Libraries Small Molecule Repository (MLSMR) to provide the Molecular Libraries Probe Production Centers Network (MLPCN) with a collection of diverse small molecules for use in high-throughput biochemical probe and drug discovery screening.¹ After completion of the initial 10 year Molecular Libraries Program (MLP), the collection
transitioned to the National Center for Advancing Translational Sciences (NCATS), and was renamed to NCATS SMR (Small Molecule Resource). 

Since its inception, the collection of almost 390,000 unique and diverse compounds has been managed in the same facility that is now part of Evotec.² One of defining criteria for the MLSMR has been its stringent QC requirements: new compounds are inspected for solubility in DMSO, and have to pass a purity cutoff of >90% by LCMS. The storage conditions are mild: nitrogen atmosphere, -20°C. Working solutions, 10mM in DMSO, undergo periodic thawing for distribution to screening centers and QC analysis is performed to verify integrity. Thus, we have accumulated over 3 million QC data points over the past 10 years.

We previously reported analysis of samples that failed QC after storage.³ Here, we applied a systematic cheminformatic approach in order to identify scaffolds that are common among such compounds.

1) http://mli.nih.gov/mli/secondary-menu/mlscn/ml-small-molecule-repository/ 
2) http://mlsmr.evotec.com 
3) Johnson, C.R. et al. Reactions during storage of the NIH Molecular Libraries Small Molecule Repository. 245th ACS Meeting, 2013, poster MEDI-127.