Discovery
The NExT Screening Libraries (Pre-plated Copies Available)
How to Access The NExT Diversity Libraries
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Submit a proposal to the NExT Program to collaborate with the Chemical Biology Consortium on an oncology-related high-throughput screen. To submit an application, please visit How to Apply.
OR
- Request a pre-plated copy of the NExT Screening Libraries for an oncology-related HTS campaign that received funding through a peer-viewed process. Please provide a brief summary of the planned screen and a summary of the peer-reviewed outcome. There is a nominal charge to cover the cost of goods and shipping. Provision of a signed copy of the Material Transfer Agreement (MTA) is also required prior to shipping. For more information please contact Dr. Barbara Mroczkowski at NCINExTinfo@mail.nih.gov.
Library Descriptions
The NExT Diversity Libraries are general screening sets that were designed to identify small molecule lead compounds for HTS drug discovery projects. These sets contain chemical scaffolds across ten commercial suppliers and contain compounds that were selected to fall within the boundaries of drug-like chemical space (e.g. Lipinski’s Rule of 5, high QED scores). All compounds passed QC (LC/MS) analysis and solubility criteria. The collections are pre-plated and include:
- Full NExT Diversity Library (83,536 cmps)
- NExT Diversity 3500 Library (3,500 cmps)
- NExT Diversity 3500 SAR Library (3,500 cmps)
In addition, the Oncology Interrogation Tools Library is available to probe mechanistic pathways and targets.
Full NExT Diversity Set
The full NExT Diversity set comprises 83,536 compounds from the three subsets outlined below. The library is pre-plated and distributed only as the combined set in 384-well single-use plates (Greiner 781280, 1uL @ 10mM in DMSO).
- Legacy Molecular Libraries Small Molecule Repository (MLSMR): 12,078 compounds
- Diversity Set 1: 47,030 compounds
- Diversity Set 2: 24,428 compounds
The Legacy MLSMR set represents a diverse subset of the MLSMR screening compound database. This database contains a variety of highly characterized screening compounds. Intense substructure filtering was applied to remove compounds with potential liabilities for drug discovery.
Diversity Sets 1 and 2 were designed around 15 privileged scaffold families (2-aminothiazole, benzoxazole, carbohydrate, chromone, coumarin, indole, isoquinoline, oxazole, phthalazin-1-one, purine, quinazoline, quinoline, quinoxaline, tetrahydroisoquinoline, and tetrahydroquinoline). Thirty-nine percent (27,880) of the compounds in Diversity Sets 1 and 2 contain one of these scaffolds. Within the respective privileged scaffold groups, compounds were clustered into smaller sub-clusters (hierarchical clustering with a cluster diameter of 0.15 using Daylight fingerprints of length 1024 bits). Small clusters with five or fewer compounds were discarded. Clusters with six or more members were retained, and six random compounds were selected. The remaining compounds in the Diversity Sets are an assorted selection from the original vendor sets.
For a detailed description about the NExT Diversity Library please see the following link: NExT Diversity Library.
Click here for an SD file that includes chemical structures, Smiles, MW, MF and NSC number.
NExT Diversity 3500 and NExT Diversity 3500 SAR Sets
These two Diversity sets are a subset of the full NExT Diversity Library, and each contains 3,500 compounds for use when utilization of the full set is not desired (e.g. lack of resources or screening validation). There is no compound overlap between the Diversity 3500 and the Diversity 3500 SAR. The libraries are pre-plated and distributed as separate sets in 384-well single-use plates (Greiner 781280, 1uL @ 10mM in DMSO).
Diversity 3500 and Diversity 3500 SAR were generated simultaneously for dual purposes. Diversity 3500 aims to broadly cover structural and physicochemical diversity, while Diversity 3500 SAR consists of compounds that, while also internally diverse, have at least five structural analogs in the Full NExT Diversity Set. The Diversity 3500 Set samples the full diversity range of the entire 83K NExT Diversity Set, while the Diversity 3500 SAR Set allows for rapid cherry-pick SAR follow-up.
Click here for an SD file that includes chemical structures, Smiles, MW, MF and NSC number.
NExT Oncology Interrogation Tools Set
The NExT Oncology Interrogation Tools library contains 555 commercially-available compounds that can be used as probes to facilitate interrogation of oncology-related biological pathways. The compounds are available arrayed on single-use plates (5uL or 10uL @ 10mM in DMSO). Approved drugs, literature compounds and newer investigational drugs that interact with intracellular signaling, growth factors and nuclear receptors are included. Annotation derived from the vendor is provided indicating the relevant molecular target/pathway for each compound.
Click here for an Excel file with the compound name and vendor-provided target/pathway information.