Selective optimization of side activities: The SOSA approach

Drug Discovery Today

Wermuth CG
Drug Discovery Today - vol. 11 160-164 (2006)

Selective optimization of side activities of drug molecules (the SOSA approach) is an intelligent and potentially more efficient strategy than HTS for the generation of new biological activities. Only a limited number of highly diverse drug molecules are screened, for which bioavailability and toxicity studies have already been performed and efficacy in humans has been […]

Benzethonium chloride: A novel anticancer agent identified by using a cell-based small-molecule screen

Clinical Cancer Research

Yip KW, Mao X, Au PYB, Hedley DW, Chow S, Dalili S, Mocanu JD, Bastianutto C, Schimmer A, Liu FF
Clinical Cancer Research - vol. 12 5557-5569 (2006)

PURPOSE:This study aims to identify a novel therapeutic agent for head and neck cancer and to evaluate its antitumor efficacy.nnEXPERIMENTAL DESIGN:A cell-based and phenotype-driven high-throughput screening of approximately 2,400 biologically active or clinically used compounds was done using a tetrazolium-based assay on FaDu (hypopharyngeal squamous cancer) and NIH 3T3 (untransformed mouse embryonic fibroblast) cells, with […]

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 […]

Development and Validation of a High-Throughput Screen for Inhibitors of SARS CoV and Its Application in Screening of a 100,000-Compound Library

Journal of Biomolecular Screening

Severson WE, Shindo N, Sosa M, Fletcher T, White EL, Ananthan S, Jonsson CB
Journal of Biomolecular Screening - vol. 12 33-40 (2006)

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)


Journal of Physiology-Paris

Shimahara T
Journal of Physiology-Paris - vol. 99 73-74 (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 […]

Integration of virtual and physical screening

Drug Discovery Today: Technologies

Fara DC, Oprea TI, Prossnitz ER, Bologa CG, Edwards BS, Sklar LA
Drug Discovery Today: Technologies - vol. 3 377-385 (2006)

High-throughput screening (HTS) represents the dominant technique for the identification of new lead compounds in current drug discovery. It consists of physical screening (PS) of large libraries of chemicals against one or more specific biological targets. Virtual screening (VS) is a strategy for in silico evaluation of chemical libraries for a given target, and can […]

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 […]