Success Stories

Potential use of alexidine dihydrochloride as an apoptosis-promoting anticancer agent.

Molecular cancer therapeutics

Yip KW, Ito E, Mao X, Au PYB, Hedley DW, Mocanu JD, Bastianutto C, Schimmer A, Liu F
Molecular cancer therapeutics - vol. 5 2234-40 (2006)

Despite advances in surgery, radiation, and chemotherapy, novel therapeutics are needed for head and neck cancer treatment. The objective of this current study was to evaluate alexidine dihydrochloride as a novel compound lead for head and neck cancers. Using a tetrazolium-based assay, the dose required to reduce cell viability by 50% (ED50) was found to […]

Cardiac glycosides provide neuroprotection against ischemic stroke: discovery by a brain slice-based compound screening platform.

Proceedings of the National Academy of Sciences of the United States of America

Wang JKT, Portbury S, Thomas MB, Barney S, Ricca DJ, Morris DL, Warner DS, Lo DC
Proceedings of the National Academy of Sciences of the United States of America - vol. 103 10461-6 (2006)

We report here the results of a chemical genetic screen using small molecules with known pharmacologies coupled with a cortical brain slice-based model for ischemic stroke. We identified a small-molecule compound not previously appreciated to have neuroprotective action in ischemic stroke, the cardiac glycoside neriifolin, and demonstrated that its properties in the brain slice assay […]

Mycophenolic acid is a potent inhibitor of angiogenesis

Arteriosclerosis, Thrombosis, and Vascular Biology

Wu X, Zhong H, Song J, Damoiseaux R, Yang Z, Lin S
Arteriosclerosis, Thrombosis, and Vascular Biology - vol. 26 2414-2416 (2006)

Probing cell-division phenotype space and Polo-like kinase function using small molecules.

Nature chemical biology

Peters U, Cherian J, Kim JH, Kwok BH, Kapoor TM
Nature chemical biology - vol. 2 618-626 (2006)

Cell-permeable small molecules that inhibit their targets on fast timescales are powerful probes of cell-division mechanisms. Such inhibitors have been identified using phenotype-based screens with chemical libraries. However, the characteristics of compound libraries needed to effectively span cell-division phenotype space, to find probes that target different mechanisms, are not known. Here we show that a […]

Identification of novel pharmacological activities of an antifungal agent, nystatin, to promote dendritic cell maturation

J Invest Dermatol

Ogawa Y, Mizumoto N, Tanaka H, Matsushima H, Takashima A
J Invest Dermatol - vol. 126 349-353 (2006)

As an unbiased functional screen to identify agents activating dendritic cells (DCs), we recently developed a DC-based biosensor system, in which a stable murine DC line XS106 was engineered to express the yellow fluorescent protein (YFP) gene under the control of the IL-1beta promoter. Here we report that nystatin (NYT), an antifungal drug of the […]

Managing, profiling and analyzing a library of 2.6 million compounds gathered from 32 chemical providers

Molecular Diversity

Monge A, Arrault A, Marot C, Morin-Allory L
Molecular Diversity - vol. 10 389-403 (2006)

The data for 3.8 million compounds from structural databases of 32 providers were gathered and stored in a single chemical database. Duplicates are removed using the IUPAC International Chemical Identifier. After this, 2.6 million compounds remain. Each database and the final one were studied in term of uniqueness, diversity, frameworks, ‘drug-like’ and ‘lead-like’ properties. This […]

Inhibition of the enzymatic activity of heme oxygenases by azole-based antifungal drugs.

The Journal of pharmacology and experimental therapeutics

Kinobe RT, Dercho RA, Vlahakis JZ, Brien JF, Szarek WA, Nakatsu K
The Journal of pharmacology and experimental therapeutics - vol. 319 277-284 (2006)

Ketoconazole (KTZ) and other azole antifungal agents are known to have a variety of actions beyond the inhibition of sterol synthesis in fungi. These drugs share structural features with a series of novel heme oxygenase (HO) inhibitors designed in our laboratory. Accordingly, we hypothesized that therapeutically used azole-based antifungal drugs are effective HO inhibitors. Using […]

Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries.

Proceedings of the National Academy of Sciences of the United States of America

Inglese J, Auld DS, Jadhav A, Johnson RL, Simeonov A, Yasgar A, Zheng W, Austin CP
Proceedings of the National Academy of Sciences of the United States of America - vol. 103 11473-11478 (2006)

High-throughput screening (HTS) of chemical compounds to identify modulators of molecular targets is a mainstay of pharmaceutical development. Increasingly, HTS is being used to identify chemical probes of gene, pathway, and cell functions, with the ultimate goal of comprehensively delineating relationships between chemical structures and biological activities. Achieving this goal will require methodologies that efficiently […]

Two approaches to drug discovery in SOD1-mediated ALS.

Journal of biomolecular screening

Broom WJ, Auwarter KE, Ni J, Russel DE, Yeh L, Maxwell MM, Glicksman M, Kazantsev AG, Brown RH
Journal of biomolecular screening - vol. 11 729-35 (2006)

Familial amyotrophic lateral sclerosis (ALS) accounts for 10% of all ALS cases; approximately 25% of these cases are due to mutations in the Cu/Zn superoxide dismutase gene (SOD1). To date, 105 different mutations spanning all 5 exons have been identified in the SOD1 gene. Mutant SOD1-associated ALS is caused by a toxic gain of function […]

Use of a fluorescent polarization based high throughput assay to identify new Calmodulin ligands

Biochimica et Biophysica Acta - Molecular Cell Research

Dagher R, Pigault C, Bonnet D, Boeglin D, Pourbaix C, Kilhoffer MC, Villa P, Wermuth CG, Hibert M, Haiech J
Biochimica et Biophysica Acta - Molecular Cell Research - vol. 1763 1250-1255 (2006)

In order to develop a fluorescence polarization (FP) assay for calcium binding proteins, a fluorescent peptides based library of 1328 compounds has been synthesized. The use of this library has been validated by setting up a FP-high-throughput screening (FP-HTS) assay for calmodulin using the synthetic gene product (synCaM). With this assay, a set of 880 […]