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Success Stories


Publications
Drug Repurposing: Far Beyond New Targets for Old Drugs

The AAPS Journal

Oprea TI, Mestres J
The AAPS Journal - vol. 14 759-763 (2012)

Repurposing drugs requires finding novel therapeutic indications compared to the ones for which they were already approved. This is an increasingly utilized strategy for finding novel medicines, one that capitalizes on previous investments while derisking clinical activities. This approach is of interest primarily because we continue to face significant gaps in the drug-target interactions matrix […]

Publications
Quantitative microtiter fibronectin fibrillogenesis assay: Use in high throughput screening for identification of inhibitor compounds

Matrix Biology

Tomasini-Johansson BR, Johnson IA, Hoffmann FM, Mosher DF
Matrix Biology - vol. 31 360-367 (2012)

Fibronectin (FN) is a plasma glycoprotein that circulates in the near micromolar concentration range and is deposited along with locally produced FN in the extracellular matrices of many tissues. The control of FN deposition is tightly controlled by cells. Agents that modulate FN assembly may be useful therapeutically in conditions characterized by excessive FN deposition, […]

Publications
Suppression of autophagy exacerbates Mefloquine-mediated cell death

Neuroscience Letters

Shin JH, Park SJ, Jo YK, Kim ES, Kang H, Park JH, Lee EH, Cho DH
Neuroscience Letters - vol. 515 162-167 (2012)

Mefloquine is an effective treatment drug for malaria. However, it can cause several adverse side effects, and the precise mechanism associated with the adverse neurological effects of Mefloquine is not clearly understood. In this study, we investigated the effect of Mefloquine on autophagy in neuroblastoma cells. Mefloquine treatment highly induced the formation of autophagosomes and […]

Publications
Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells

Cell

Sachlos E, Risueño RM, Laronde S, Shapovalova Z, Lee JH, Russell J, Malig M, McNicol JD, Fiebig-Comyn A, Graham M, Levadoux-Martin M, Lee JB, Giacomelli AO, Hassell JA, Fischer-Russell D, Trus MR, Foley R, Leber B, Xenocostas A, Brown ED, Collins TJ, Bhatia M
Cell - vol. 149 1284-1297 (2012)

Selective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from […]

Publications
Mitochondrial fragmentation caused by phenanthroline promotes mitophagy

FEBS Letters

Park SJ, Shin JH, Kim ES, Jo YK, Kim JH, Hwang JJ, Kim JC, Cho DH
FEBS Letters - vol. 586 4303-4310 (2012)

Mitochondrial dynamics and mitophagy are thought to be important events for the quality control of mitochondria and mitochondria-associated diseases. To identify novel mitophagy modulators, we developed a cell-based screening system and selected 1,10-phenanthroline (Phen) as a target molecule. Phen treatment highly induced mitochondrial fragmentation and mitochondrial dysfunctions in a Drp1 dependent manner. Phen treatment also […]

Publications
Signaling property study of adhesion G-protein-coupled receptors

FEBS Letters

Gupte J, Swaminath G, Danao J, Tian H, Li Y, Wu X
FEBS Letters - vol. 586 1214-1219 (2012)

Adhesion G-protein-coupled receptors (GPCR) are special members of GPCRs with long N-termini containing multiple domains. We overexpressed our collection of receptors together with G-proteins in mammalian cell lines and measured the concentrations of intracellular signaling molecules, such as inositol phosphate and cAMP. Our results show that a subset of tested adhesion GPCRs has constitutive activities […]

Publications
New horizons for antiviral drug discovery from virus-host protein interaction networks

Current Opinion in Virology

De Chassey B, Meyniel-Schicklin L, Aublin-Gex A, André P, Lotteau V
Current Opinion in Virology - vol. 2 606-613 (2012)

Viruses are recurrent socio economical and health problems each year worldwide. Current drugs are mainly directed against viral components and select resistant strains that urge the need to develop new antiviral therapeutics. High-throughput screening technologies now allow to draw comprehensive genome-wide maps of physical and genetic virus-host interactions. This has been done recently for several […]

Publications
Identification of Specific Pluripotent Stem Cell Death-Inducing Small Molecules by Chemical Screening

Stem Cell Reviews and Reports

Conesa C, Doss MX, Antzelevitch C, Sachinidis A, Sancho J, Carrodeguas JA
Stem Cell Reviews and Reports - vol. 8 116-127 (2012)

A potential application of embryonic and inducible pluripotent stem cells for the therapy of degenerative diseases involves pure somatic cells, free of tumorigenic undifferentiated embryonic and inducible pluripotent stem cells. In complex collections of chemicals with pharmacological potential we expect to find molecules able to induce specific pluripotent stem cell death, which could be used […]

Publications
Potential Repurposing of Known Drugs as Potent Bacterial -Glucuronidase Inhibitors

Journal of Biomolecular Screening

Ahmad S, Hughes MA, Yeh L, Scott JE
Journal of Biomolecular Screening - vol. 17 957-965 (2012)

The active metabolite of the chemotherapeutic irinotecan, SN-38, is detoxified through glucuronidation and then excreted into the gastrointestinal tract. Intestinal bacteria convert the glucuronidated metabolite back to the toxic SN-38 using β-glucuronidase (GUS), resulting in debilitating diarrhea. Inhibiting GUS activity may relieve this side effect of irinotecan. In this study, we sought to determine whether […]

Publications
A small molecule screen in yeast identifies inhibitors targeting protein-protein interactions within the vaccinia virus replication complex

Antiviral Research

Flusin O, Saccucci L, Contesto-Richefeu C, Hamdi A, Bardou C, Poyot T, Peinnequin A, Crance JM, Colas P, Iseni F
Antiviral Research - vol. 96 187-195 (2012)

Genetic and biochemical data have identified at least four viral proteins essential for vaccinia virus (VACV) DNA synthesis: the DNA polymerase E9, its processivity factor (the heterodimer A20/D4) and the primase/helicase D5. These proteins are part of the VACV replication complex in which A20 is a central subunit interacting with E9, D4 and D5. We […]