Tumor Hsp90 Inhibitor

To identify novel tumor Hsp90 inhibitors with potential for use in cancer therapy and in the treatment of neurodegenerative diseases.

DNA-polymerase III (polymerase core enzme) inhibitor

1. Transfer and run the HTS assay for the DNA polymerase III Holoenzyme (Pol III HE) from the representative Gram (-) model organism E. coli. 2. Prioritize compounds identified via HTS of the MLSCN library for further chemical optimization and development.

qHTS Assay for Disrupters of an Hsp90 Co-Chaperone Interaction

DNA Primase Inihibitor

1. Transfer and run the HTS assay for the DNA polymerase III Holoenzyme (Pol III HE) from the representative Gram (-) model organism E. coli. 2. Prioritize compounds identified via HTS of the MLSCN library for further chemical optimization and development.

Ikappa-B-alpha stabilizers in a human lymphoma cell line

Splicing modulators at the Beta Globin locus

Identify small-molecule modulators of Beta-Globin splicing by high throughput screening of chemical libraries.

Tau Filament Binding

Identify ligands capable of binding amyloidgenic tau conformations with high affinity.

Epigenetic Modulators

Identify small-molecule modulators of cellular epigenetic pathways

Epigenetic Modulators

Identify small-molecule modulators of cellular epigenetic pathways

Epigenetic Modulators

Identify small-molecule modulators of cellular epigenetic pathways

Agonists of the Thyroid Stimulating Hormone Receptor

Identify small-molecule agonists of the Thyroid Stimulating Hormone Receptor.

Inhibitor of the Mevalonate Pathway in Streptococcus pneumoniae 1: Inhibitors of Mevalonate Kinase (MK)

To identify specific probes that inhibit the MK enzyme, the first of three enzymes in the mevalonate pathway of S. pneumoniae.

Pantothenate Synthetase (PanC) Inhibitor

To identify specific probes that inhibit the Mycobacterium tuberculosis pantothenate synthetase enzyme for X-ray crystallographic studies

S1P1 Antagonist

Identify compounds which provide insight into the molecular mechanism of S1P biological function.

High Throughput Fluorescence Polarization Screen for Bcl-B Phenotypic Converters

To identify small molecule chemical probes that bind to Bcl-B within its TR3-binding site.

Autoinducing pheromone (AIP)-dependent bacterial quorum sensing: AIP binding target

1. To screen libraries of small molecules in a high throughput fluorescence-based screening assay to identify compounds capable of suppressing pheromone-dependent activation of the promoter for a global regulator of Staphylococcus aureus virulence, RNAIII. 2. To confirm that the compounds that inhibit RNAIII promoter activation also inhibit expression of the virulence genes that are regulated by RNAIII.

Autoinducing pheromone (AIP)-dependent bacterial quorum sensing of S. aureus Agr3 agr locus genotype: target downstream of AIP binding

1. To screen libraries of small molecules in a high throughput fluorescence-based screening assay to identify compounds capable of suppressing pheromone-dependent activation of the promoter for a global regulator of Staphylococcus aureus virulence, RNAIII. 2. To confirm that the compounds that inhibit RNAIII promoter activation also inhibit expression of the virulence genes that are regulated by RNAIII.

Formylpeptide Receptor (FPR) Antagonist

Formylpeptide Receptor-Like 1 (FPRL-1) Antagonist

Competitive inhibitor of lingand binding for G protein-coupled receptor 30 (GPR30)

To identify small molecule ligands specific for GPR30 or the classical estrogen receptors (ER? and ER?).

Competitive inhibitor of lingand binding for G protein-coupled receptor 30 (GPR30)

To identify small molecule ligands specific for GPR30 or the classical estrogen receptors (ER? and ER?).

Activator of Prostate Cell Differentiation

1. To screen for small molecules that modulate prostate cell differentiation, using HyperCyt® high throughput (HT) flow cytometry. 2. To counter-screen active compounds identified in the primary and confirmatory screens in LNCaP cells in a similar dose response assay using PC-3 cells to identify small molecules that induce intracellular granularity in an androgen-independent manner.

Ruthenium-based TrkA Inhibitor

To design potent, specific, and novel Ruthenium-based small-molecule inhibitors of the protein kinase TrkA.

Aggregation and Clearance of Huntingtin Inclusions: Huntington’s Disease Assay

Protein Kinase D Inhibitor

To identify small molecule inhibitors of PKD

Inhibitors of the Polo box domain of Human Polo-like kinase 1

1. Screen MLSCN compound libraries for inhibitors of the polo box domain of polo-like kinase-1 (Plk-1-PBD) using a high throughput-ready fluorescence polarization (FP) assay. 2. Follow up primary screen of PBD inhibitors with secondary biochemical and cell based assays to confirm hits.

Inhibitor of anti-apoptotic protein Bfl-1

To identify chemical probes of Bfl-1 through a fluorescence polarization assay (FPA) using FITC-Bid BH3 peptide.

Inhibitor of anti-apoptotic protein Bfl-1

To identify chemical probes of Bfl-1 through a fluorescence polarization assay (FPA) using FITC-Bid BH3 peptide.

EphA4 Receptor Antagonists for Nervous System Repair

To identify small molecule antagonists that inhibit the binding of EphA4 to the KYL peptide which interacts with high affinity to the ephrin-binding site of EphA4.

Chemical Inhibitors of ER Stress

To identify compounds that selectively inhibit cell death induced by endoplasmic reticulum (ER) stress in mammalian cells.

Tissue-nonspecific Alkaline Phosphatase (TNAP)

To identify novel highly potent and selective inhibitors of TNAP which to date have not been available.

Intestinal alkaline phosphatase (IAP-L) Inhibitor

To identify inhibitors of intestinal alkaline phosphatase (IAP) that show selectivity for the target over the other alkaline phosphatase isozymes (PLAP, TNAP).

Human Cathepsin L Inhibitor

To perform a high throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) to identify novel, potent, and selective inhibitors of human cathepsin L.

N-(quinolin-8-yl)benzenesulfonamides as Agents Capable of Down-Regulating NF?B Activity within Two Separate High-Throughput Screens of NF?B Activation

To identify specific compounds that inhibit signaling mediated by NF?B after stimulation of human umbilical vein endothelial cells (HUVEC) by TNFalpha

Matrix Metalloproteinase-8 (MMP-8) Inhibitor

To identify selective chemical inhibitors of MMP-8

Matrix Metalloproteinase-13 (MMP-13) Inhibitor

To identify selective chemical inhibitors of MMP-13

Matrix Metalloproteinase-13 (MMP-13) Inhibitor

To identify selective chemical inhibitors of MMP-13

Sphingosine-1-phosphate receptor 2 (S1P2) Agonist

To identify specific agonists of the S1P2 receptor

Phosphodiesterase 4 (PDE4) Inhibitor in the cyclic response element-binding proteins (CREB) pathway

Chemical inhibitors of antigen receptor-induced NF-?B

To identify compounds that selectively inhibit one of the several known pathways that lead to NF-kB activation in mammalian cells.

Tissue-nonspecific Alkaline Phosphatase (TNAP)

To identify novel highly potent and selective inhibitors of TNAP which to date have not been available.

High Throughput Screening Campaign to Identify Inhibitors of MMP-8

To identify selective exosite/active site inhibitors of A Disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4)

AmpC beta-lactamase Non-Covalent Inhibitor

To identify novel inhibitors (both covalent and non-covalent) of the AmpC B-lactamase enzyme class.

AmpC beta-lactamase Covalent Inhibitor

To identify novel inhibitors (both covalent and non-covalent) of the AmpC B-lactamase enzyme class.

Human Cathepsin L Inhibitor

To perform a high throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) to identify novel, potent, and selective inhibitors of human cathepsin L.

Inhibitors of the NS2B-NS3 Proteinase of West Nile Virus

Identify drug-like small molecule inhibitors of the NS3 West Nile virus protease by high throughput screening of chemical libraries.

12-kDa FK506-binding protein (FKBP12) Activator

Identify novel chemical probes that target FKBP12

Toll-Like Receptor 4-MyD88 Signaling Inhibitor

To identify inhibitors of TLR4 signaling

Measles Virus Inhibitor

1. To identify novel MV-specific probes through high throughput screening (HTS) of the MLSCN library. 2. To counterscreen putative probes in independent assays and rank confirmed hits by active concentration and cytotoxicit. 3. To determine the specificity of selected probes and assess their mechanisms of antiviral activity

High-Throughput Screening Campaign to Identify Inhibitors of SF-1

To identify selective cell-permeable inhibitors of the steroidogenic factor 1

High-Throughput Screening Campaign to Identify Inhibitors of SF-1

To identify modular, chemically tractable, selective, and cell-permeable inverse agonists of the nuclear receptor RAR.

High-Throughput Screening Campaign to Identify Inhibitors of SF-1

To identify selective cell-permeable inhibitors of the steroidogenic factor 1 (orphan nuclear receptor NR5A1)

HIV-1 Reverse Transcriptase Associated Ribonuclease H (Rnase H) Inhibitor

Zebrafish Angiogenesis Inhibitor

To discover novel angiogenesis inhibitors using live zebrafish embryos.

Rho Kinase II Inhibitor

To find potent inhibitors for Rho-Kinase. “Kinase-Glo”, an ATP depletion assay was used to find inhibitors that are specific to the ATP binding site.

CREB signaling pathway: CRE potentiator

Identify small molecular potentiators of the CREB pathway for memory and cognitive disorders using quantitative high throughput screening (qHTS).

Molecule Modulators: Voltage-Dependent Potassium (RMI)

To identify small molecule modulators of KvBeta that are cell permeable and have a Km sufficient for in vitro cellular physiology assays.

Allosteric Modulators of the M1 Muscarinic Receptor - Antagonist

To identify small molecule modulators of M1 muscarinic receptor that are cell permeable, exhibit micromolar potency, and show greater than 10 fold selectivity over other muscarinic family members M2, M3, M4 and M5.

Sphingosine-1-phosphate receptor 1 (S1P1) Agonist

Identify compounds which provide insight into the molecular mechanism of S1P biological function.

Sphingosine-1-phosphate receptor 3 (S1P3) Agonist

Identify compounds which provide insight into the molecular mechanism of S1P biological function.

Sphingosine-1-phosphate receptor 3 (S1P3) Agonist

Identify compounds which provide insight into the molecular mechanism of S1P biological function.

Sphingosine-1-phosphate receptor 3 (S1P3) Agonist

Identify compounds which provide insight into the molecular mechanism of S1P biological function.

Sphingosine-1-phosphate receptor 3 (S1P3) Agonist

Identify compounds which provide insight into the molecular mechanism of S1P biological function.

Glucocerebrosidase Inhibitor (Chemotype 3)

Glucocerebrosidase Inhibitor (Chemotype 2)

Glucocerebrosidase Inhibitor (Chemotype 1)

Inhibitor of Schistosoma Mansoni Redox Cascade

Inhibitor of Bacillus stearothermophilus Pyruvate Kinase