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Chemical and RNAi Libraries

Dharmacon siGENOME siRNA Library

 

Figure 1

The Dharmacon SMARTpool® siRNA Library has 4 siRNA duplexes in each well, all targeting the same gene. According to Dharmacon: “Each SMARTpool reagent and 3 of 4 individual duplexes are guaranteed to silence target gene expression at the mRNA level by at least 75% when used under optimized transfection and detection conditions.” Once screening hits are identified, individual duplexes can be purchased for hit confirmation. The siRNA Library is separated into 10 “functional” lots, e.g., kinases or GPCRs, with the number of gene targets indicated in the Table.

 

Three control siRNAs have been included on each plate and the remaining wells in the first two columns and the last two columns have been left empty for positive and negative controls specific to the assay. The three controls include: 

  • Human PLK1 SMARTpool: Positive control; knockdown of polo-like kinase 1 results in apoptosis in most cell lines; should cause cell death if transfection is efficient
  • siGENOME Non-Targeting siRNA #2: Negative control; contains at least four mismatches to all known human, mouse and rat genes; should not effect cell viability; intended to confirm that cells are not affected by the transfection reagent or assay conditions
  • siGLO RISC-Free Control siRNA: Positive control for transfection; stable, fluorescent, non-targeting control siRNA with RISC-Free modification; intended to confirm siRNA transfection using a fluorescence microscope. This control also enables co-transfection with functional siRNA without interfering with target gene silencing.  

 

Specialized Libraries 

 

Enzo Screen-Well Bioactive Lipid Library (received November 2013)

The Screen-Well™ Bioactive Lipid Library contains 195 bioactive lipids in a 96 well format for screening or identifying recombinant orphan G protein-coupled receptors, target validation, secondary screening, validating new assays and for routine pharmacological applications.  Includes: Endocannabinoids, Farnesyl/geranylgeranyl derivatives, HETEs, deHETEs, hepoxilins, Polyunsaturated fatty acids, Leukotrienes, lipoxins, LPA and phosphatidic acids, Octadecanoids, PAFs, Prostaglandins and thromboxanes, Retinoids, vitamin D metabolites, Sphingolipids.

 

GlaxoSmithKline (GSK) Protein Kinase Inhibitor Set (received March 2013)
The Protein Kinase Inhibitor Set (PKIS) consists of 367 small molecule kinase inhibitors that have been published by GSK. These compounds cover a range of chemotypes as well as multiple exemplars within a given chemotype; in addition a range of kinase targets and selectivity profiles are represented. The PKIS have been characterized across a panel of 220 kinase assays. A pdf of structures and targets is available upon request to SMSSF.

 

NCI

The NCI04 "Diversity Set III" library (received 10-18-2012) consists of 1597 compounds.

 

The NCI05 "Mechanistic Diversity Set" library (received 10-18-2012) consists of 879 compounds which have represent a broad range of structural diversity and patterns of growth inhibition in the NCI 60 cell line screen.

 

The NCI06 "Natural Product Set II" library (received 10-18-2012) consists of 117 natural products that were selected from the NCI open repository.

 

The NCI07 "Approved Oncology Set IV" library (received 10-18-2012) includes 101 compounds.

 

More information about these libraries can be found on the NCI/NIH Developmental Therapeutics Program website for Synthetics and Pure National Products Repositories and Basic Chemical Data.

 

NIH Clinical Collection

The NIH Clinical Collection (NCC) is a plated array of approximately 450 small molecules that have a history of use in human clinical trials. Similar collections of FDA approved drugs have proven to be rich sources of undiscovered bioactivity and therapeutic potential. The clinically tested compounds in the NCC are highly drug-like with known safety profiles. These compounds can provide excellent starting points for medicinal chemistry optimization and, for high-affinity targets, may even be appropriate for direct human use in new disease areas.

 

Selleck Kinase Inhibitor Library (received November 2013)

The Selleck Kinase Inhibitor Library is a unique collection of 273 kinase inhibitors for high throughput screening (HTS) and high content screening (HCS)

  • Bioactivity and safety confirmed by preclinical research and clinical trials
  • Some inhibitors have been approved by the FDA
  • Targets kinases such as RTKs, PI3K, Aurora Kinase, CDK, and MEK
  • Most are ATP competitive
  • Structurally diverse, medicinally active and cell permeable
  • Rich documentation with structure, IC50, and customer reviews
  • NMR and HPLC validated to ensure high purity 

Prestwick Chemical Library

The Prestwick Chemical Library® contains 1120 small molecules, 100% being marketed drugs, thus it presents the greatest possible degree of drug-likeliness. The active compounds were selected for their high chemical and pharmacological diversity as well as for their known bioavailability and safety in humans.

 

The Spectrum Collection

The 2000 compounds in the SPECTRUM Collection were selected by medicinal chemists and biologists to provide a wide range of biological activities and structural diversity for screening programs with special emphasis on the de-novo assays emerging today. Such content provides the opportunity to evaluate drugs and biochemical tools with known biological profiles and, at the same time, explore the potential of novel structural and topographical diversity manifest in pure natural products.


 

Diversity Libraries

 

ChemBridge

The facility possesses a 16,000 compound library from the ChemBridge DIVERSet. These are a collection of "universally" diverse, pre-designed drug-like small molecules.  The compounds have been rationally selected based on 3D pharmacophore analysis to cover the broadest part of biologically relevant pharmacophore diversity space. 

 

Chemical Diversity Labs

This library is a 20,000 member compound library from Chemical Diversity Labs. This library was chosen to complement the Chembridge library. 

 

Life Chemicals

The Life Chemicals diversity libraries (LifeCHEMI and LifeCHEM2) consist of 50,000 diverse, drug-like compounds selected from Life Chemicals, Inc. repository. Life Chemicals maintains that "All compounds in our Collection can be distinguished as original, most carefully selected, diverse, well-characterised and pure, lead-like and drug-like new chemical entities". 

 

Maybridge

The Maybridge HitFinder collection of screening compounds consists of 14,400 premier compounds representing the drug-like diversity of the Maybridge Screening Collection, offering easy and rapid lead identification. All screening compounds fit Lipinski guidelines for "drug-likeness", and all have purity greater than 90%. The compounds are arrayed in 45 384-well microtiter plates and are available for screening at 1mM and 0.1mM stock concentrations. The first and last two columns are empty on each plate.