This plated set (2 microtiter plates/set) contains most current FDA-approved anticancer drugs. The current set (AODVI) consists of 119 agents and is intended to enable cancer research, drug discovery and combination drug studies. Details on the drugs included in this plated set can be found by clicking on Approved Oncology Drugs Plated Set (Plate 1, Plate 2). Compounds in this set are provided as 20 microliters at 10mM in 100% DMSO; plates are shipped frozen, with dry ice. All proprietary agents in this set were obtained through commercial sources. All compounds were found to have satisfactory purity and identity. In general, substances were checked by both NMR and LC-MS. For recently-acquired compounds, the supplier's Certificate of Analysis was accepted.
The NCI Diversity Set IV of 1596 compounds is available on Greiner 650201 96-well PP U-bottom plates. Compounds are arrayed at 20 uL /10 mM in DMSO.
The NCI Diversity Set IV was derived from the almost 140,000 compounds available for distribution from the DTP repository. Only compounds having at least 250 mg of material available were considered. The final set was selected using the programs Chem-X (Oxford Molecular Group) and Catalyst (Accelrys, Inc.). that use defined pharmacophoric centers (i.e., hydrogen bond acceptor, hydrogen bond donor, positive charge, aromatic, hydrophobic, acid, base) and defined distance intervals to create a finite set of three dimensional, 3-point pharmacophores resulting in over 1,000,000 possible pharmacophores for the Diversity Set IV selection. The selection protocol considered each molecule, all its pharmacophores and each of its conformational isomers. During the generation of the diversity set, the pharmacophores for any candidate compound were compared to the set of all pharmacophores found in structures already accepted into the set. If the current structure had more than 5 new pharmacophores, it was added to the set. An additional objective was to create a diverse set of compounds that were amenable to forming structure-based hypotheses. Thus, molecules that were relatively rigid, with 5 or fewer rotatable bonds, having a tendency to be planar, 1 or less chiral centers, and pharmacologically desirable features (i.e., did not contain: obvious leaving groups, weakly bonded heteroatoms, organometallics, polycyclic aromatic hydrocarbons, etc.) were given priority in the final selection. This resulted in a set of 1596 compounds. All compounds were checked for purity via LC/Mass Spec. and found to have a purity of 90% or better by this method.
The Mechanistic Set III is available on Greiner 650201 96-well PP U-bottom plates. Compounds are arrayed at 20 μL/1 mM in DMSO.
The Mechanistic Set III, which consists of 813 compounds, was derived from the 37,836 open compounds that have been tested in the NCI human tumor 60 cell line screen. In contrast to the original diversity set of 1,990 compounds, which was chosen on the basis of structural diversity, this mechanistic diversity set was chosen to represent a broad range of growth inhibition patterns in the 60 cell line screen, based on the GI50 activity of the compounds. Compounds that have been tested in the 60 cell line screen were clustered using the FASTCLUS procedure in the SAS statistical package. This algorithm is based on MacQueen’s k-means algorithm, which minimizes the sum of squared distances from the cluster means. The procedure resulted in 1272 clusters. A single representative compound from each cluster, for which an adequate supply of material was available, was chosen. Some clusters are not represented in the set, as insufficient material was available.
The Natural Products Set III (successor to the original Natural Products Set II) consists of 117 compounds that were selected from the DTP Open Repository collection of 140,000 compounds. Factors in selection were origin, purity (>90% by ELSD, major peak has correct mass ion), structural diversity and availability of compound. This set was created in response to numerous drug discovery research groups that expressed a desired to study a variety of scaffold structures having multiple functional groups.
The compounds are in 96-well polypropylene (PP) microtiter plates with 60 compounds per plate. The outside rows and columns of each plate are left empty. Plates are stored dry at -20°C. Each well contains 0.20 µMol of compound plus 1 µL of glycerol; 20 µL of a 10mM solution of each compound can be obtained by the addition of 19 µL of DMSO to each well. It is recommended that solubilization be done immediately before testing. If this is not possible, promptly replicate the drug solutions into several testing plates, as there is ample history of compounds at 10mM in DMSO precipitating from solution and not easily resolubilized.