success-story

Success Stories


Publications
Discovery of novel cyclophilin A ligands using an H/D exchange- and mass spectrometry-based strategy.

Journal of biomolecular screening

Dearmond PD, West GM, Anbalagan V, Campa MJ, Patz EF, Fitzgerald MC
Journal of biomolecular screening - vol. 15 1051-62 (2010)

Cyclophilin A (CypA) is an overexpressed protein in lung cancer tumors and as a result is a potential therapeutic and diagnostic target. Described here is use of an H/D exchange- and a matrix assisted laser desorption/ionization (MALDI) mass spectrometry-based assay, termed single-point SUPREX (Stability of Unpurified Proteins from Rates of H/D Exchange), to screen 2 […]

Publications
High-content screening of feeder-free human embryonic stem cells to identify pro-survival small molecules.

The Biochemical journal

Andrews PD, Becroft M, Aspegren A, Gilmour J, James MJ, McRae S, Kime R, Allcock RW, Abraham A, Jiang Z, Strehl R, Mountford JC, Milligan G, Houslay MD, Adams DR, Frearson JA, Watanabe K, Ueno M, Kamiya D, Nishiyama A, Matsumura M, Wataya T, Takahashi J, Nishikawa S, Nishikawa S, Muguruma K, Sasai Y, Claassen D, Desler M, Rizzino A, Li X, Meng G, Krawetz R, Liu S, Rancourt D, Krawetz R, Li X, Rancourt D, Olson M, Davies S, Reddy H, Caivano M, Cohen P, Darenfed H, Dayanandan B, Zhang T, Hsieh S, Fournier A, Mandato C, Liu Y, Song Z, Zhao Y, Qin H, Cai J, Zhang H, Yu T, Jiang S, Wang G, Ding M, Deng H, Brenk R, Schipani A, James D, Krasowski A, Gilbert I, Frearson J, Wyatt P, Zhang J, Chung T, Oldenburg K, Grover G, Nichols R, Dzamko N, Hutti J, Cantley L, Deak M, Moran J, Bamborough P, Reith A, Alessi D, Takami A, Iwakubo M, Okada Y, Kawata T, Odai H, Takahashi N, Shindo K, Kimura K, Tagami Y, Miyake M, Yamaguchi H, Miwa Y, Kasa M, Kitano K, Amano M, Kaibuchi K, Hakoshima T, Jacobs M, Hayakawa K, Swenson L, Bellon S, Fleming M, Taslimi P, Doran J, Yamaguchi H, Kasa M, Amano M, Kaibuchi K, Hakoshima T, Iwakubo M, Takami A, Okada Y, Kawata T, Tagami Y, Ohashi H, Sato M, Sugiyama T, Fukushima K, Iijima H, Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh B, Hubbard S, Schlessinger J, Ardehali H, O'Rourke B, Laflamme M, Chen K, Naumova A, Muskheli V, Fugate J, Dupras S, Reinecke H, Xu C, Hassanipour M, Police S, Pasquale E, Wang X, Lin G, Martins-Taylor K, Zeng H, Xu R, Xu Y, Zhu X, Hahm H, Wei W, Hao E, Hayek A, Ding S, Vallier L, Alexander M, Pedersen R, Annerén C, Cowan C, Melton D, Meyn M, Schreiner S, Dumitrescu T, Nau G, Smithgall T, Barbaric I, Gokhale P, Jones M, Glen A, Baker D, Andrews P
The Biochemical journal - vol. 432 21-33 (2010)

The propensity of human embryonic stem cells to die upon enzymatic disaggregation or low-density plating is an obstacle to their isolation and routine use in drug discovery and basic research. Equally, the very low rate of establishment of implanted cells hinders cell therapy. In the present study we have developed a high-content assay for human […]

Publications
Identification of Translational Activators of Glial Glutamate Transporter EAAT2 through Cell-Based High-Throughput Screening: An Approach to Prevent Excitotoxicity

Journal of Biomolecular Screening

Colton CK, Kong Q, Lai L, Zhu MX, Seyb KI, Cuny GD, Xian J, Glicksman MA, Glenn Lin C
Journal of Biomolecular Screening - vol. 15 653-662 (2010)

Publications
Identification by high-throughput screening of inhibitors of Schistosoma mansoni NAD+ catabolizing enzyme

Bioorganic and Medicinal Chemistry

Kuhn I, Kellenberger E, Said-Hassane F, Villa P, Rognan D, Lobstein A, Haiech J, Hibert M, Schuber F, Muller-Steffner H
Bioorganic and Medicinal Chemistry - vol. 18 7900-7910 (2010)

Schistosomiasis is a major tropical parasitic disease. For its treatment, praziquantel remains the only effective drug available and the dependence on this sole chemotherapy emphasizes the urgent need for new drugs to control this neglected disease. In this context, the newly characterized Schistosoma mansoni NAD+ catabolizing enzyme (SmNACE) represents a potentially attractive drug target. This […]

Publications
Detection of intracellular granularity induction in prostate cancer cell lines by small molecules using the HyperCyt high-throughput flow cytometry system.

Journal of biomolecular screening

Haynes MK, Strouse JJ, Waller A, Leitao A, Curpan RF, Bologa C, Oprea TI, Prossnitz ER, Edwards BS, Sklar LA, Thompson TA
Journal of biomolecular screening - vol. 14 596-609 (2009)

Prostate cancer is a leading cause of death among men due to the limited number of treatment strategies available for advanced disease. Discovery of effective chemotherapeutics involves the identification of agents that inhibit cancer cell growth. Increases in intracellular granularity have been observed during physiological processes that include senescence, apoptosis, and autophagy, making this phenotypic […]

Publications
Quantitative high-throughput screening identifies inhibitors of anthrax-induced cell death

Bioorganic and Medicinal Chemistry

Zhu PJ, Hobson JP, Southall N, Qiu C, Thomas CJ, Lu J, Inglese J, Zheng W, Leppla SH, Bugge TH, Austin CP, Liu S
Bioorganic and Medicinal Chemistry - vol. 17 5139-5145 (2009)

Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a β-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin […]

Publications
Identification and characterization of novel sirtuin inhibitor scaffolds

Bioorganic and Medicinal Chemistry

Sanders BD, Jackson B, Brent M, Taylor AM, Dang W, Berger SL, Schreiber SL, Howitz K, Marmorstein R
Bioorganic and Medicinal Chemistry - vol. 17 7031-7041 (2009)

The sirtuin proteins are broadly conserved NAD+-dependent deacetylases that are implicated in diverse biological processes including DNA recombination and repair, transcriptional silencing, longevity, apoptosis, axonal protection, insulin signaling, and fat mobilization. Because of these associations, the identification of small molecule sirtuin modulators has been of significant interest. Here we report on high throughput screening against […]

Publications
Deciphering the antitumoral activity of quinacrine: Binding to and inhibition of Bcl-xL

Bioorganic and Medicinal Chemistry Letters

Orzáez M, Mondragón L, García-Jareño A, Mosulén S, Pineda-Lucena A, Pérez-Payá E
Bioorganic and Medicinal Chemistry Letters - vol. 19 1592-1595 (2009)

From the screening of a unique collection of 880 off-patent small organic molecules, we have found that quinacrine inhibits the interaction between a BH3 domain-derived peptide and the antiapoptotic protein Bcl-xL. Nuclear magnetic resonance spectroscopy confirmed that quinacrine binds to the hydrophobic groove that Bcl-xL uses for interacting with the BH3 domain of proapoptotic proteins. […]

Publications
Simulating henipavirus multicycle replication in a screening assay leads to identification of a promising candidate for therapy.

Journal of Virology

Porotto M, Orefice G, Yokoyama CC, Mungall BA, Realubit R, Sganga ML, Aljofan M, Whitt M, Glickman F, Moscona A
Journal of Virology - vol. 83 5148-5155 (2009)

Nipah (NiV) and Hendra (HeV) viruses are emerging zoonotic paramyxoviruses that cause encephalitis in humans, with fatality rates of up to 75%. We designed a new high-throughput screening (HTS) assay for inhibitors of infection based on envelope glycoprotein pseudotypes. The assay simulates multicycle replication and thus identifies inhibitors that target several stages of the viral […]

Publications
Automated high-content screening for compounds that disassemble the perinucleolar compartment.

Journal of biomolecular screening

Norton JT, Titus SA, Dexter D, Austin CP, Zheng W, Huang S
Journal of biomolecular screening - vol. 14 1045-1053 (2009)

All solid malignancies share characteristic traits, including unlimited cellular proliferation, evasion of immune regulation, and the propensity to metastasize. The authors have previously described that a subnuclear structure, the perinucleolar compartment (PNC), is associated with the metastatic phenotype in solid tumor cancer cells. The percentage of cancer cells that contain PNCs (PNC prevalence) is indicative […]