NExT Screening Libraries
All requests and distributions of the NExT Screening Libraries are on hold until further notice.
The NExT Program has assembled a number of compound library collections that include Diversity, Focused Targeted, and Focused Non-Targeted screening sets.
Within the collections are four Diversity collections that include:
- 83K Full NExT Diversity set
- 142K Legacy Diversity set, derived from the Molecular Library Small Molecule Repository screening set
- Pilot Diversity set of 3500 compounds representing a broad subset of the 83K NExT Diversity set
- Pilot SAR Diversity set of 3500 compounds representing distinct privileged scaffolds within the Full NExT Diversity set that are intended to impart SAR trends.
The Focused Target sets comprise target classes such as kinase, G-protein coupled receptor (GPCR), protein-protein-interactions (PPIs), ion channel, proteases, etc. Each focus target set may contain from 1-5 different collections containing a few dozen to several hundreds of compounds. None of the sets are available as pre-plated copies. They require preparation of plates after appropriate approvals from NCI, such as through an accepted NExT application
The Focused Non-Target sets include compound classes such as fragments, pharma collections, natural products, macrocycles, and Oncology Interrogation tool sets. The latter of these currently has pre-plated copies available for distribution, pending approval by the NCI, through an accepted NExT application, for example.
Accessing the NExT Libraries
Parties interested in obtaining copies of the NExT Diversity Library may do so in one of two ways, as described below:
- Submit a NExT application and proposal to collaborate with the Chemical Biology Consortium on an oncology-related high-throughput screen.
- Request a pre-plated copy of the NExT Screening Libraries for an oncology-related HTS campaign that received funding through a peer-reviewed process. As part of the request, please provide a brief summary of the planned screen and a summary of the peer-reviewed outcome, including the awarded grant reference number. There is a nominal charge to cover the cost of goods and shipping. Provision of a signed copy of the NExT Material Transfer Agreement (MTA) is also required prior to shipping. All requests should be emailed to the NExT Info Mail (NCINExTinfo@mail.nih.gov).
Downloadable Files
The NExT Program offers interested parties downloadable SD Files for the Full NExT, Diversity pilot 3500, and SAR pilot 3500 sets. Please use the links below to download the SD Files:
In addition, the Oncology Interrogation Tools Library is available to probe mechanistic pathways and targets. The composition of the library can be viewed by downloading the file below:
Description of Available Pre-plated Libraries
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 Properties and Metrics
NExT Diversity 3500 and NExT Diversity 3500 SAR Pilot Sets
These two Diversity sets are a subset of the full NExT Diversity Library, and each contains 3,500 compounds for use when use of the full set is not desired (e.g., there is a 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.
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.