Publications


Publications
High throughput screening for small molecule inhibitors of heparin-induced tau fibril formation

Biochemical and Biophysical Research Communications

Crowe A, Ballatore C, Hyde E, Trojanowski JQ, Lee VM
Biochemical and Biophysical Research Communications - vol. 358 1-6 (2007)

A library of ∼51,000 compounds was interrogated by high throughput screening (HTS) using a heparin-induced tau fibrillization assay. HTS was conducted with bacterially expressed recombinant tau fragment K18 and the reaction was monitored by thioflavine T fluorescence. Hits meeting criteria set for selection in HTS were further evaluated in a panel of assays designed (a) […]

Publications
Modeling promiscuity based on in vitro safety pharmacology profiling data

ChemMedChem

Azzaoui K, Hamon J, Faller B, Whitebread S, Jacoby E, Bender A, Jenkins JL, Urban L
ChemMedChem - vol. 2 874-880 (2007)

This study describes a method for mining and modeling binding data obtained from a large panel of targets (in vitro safety pharmacology) to distinguish differences between promiscuous and selective compounds. Two naïve Bayes models for promiscuity and selectivity were generated and validated on a test set as well as publicly available drug databases. The model […]

Publications
High-Troughput Identification of Inhibitors of Human Mitochondrial Peptide Deformylase

J. Biomol. Screen

Antczak C, Shum D, Escobar S, Bassit B, Seshan VE, Wu N, Yang G, Li Y, Scheinberg DA, Djaballah H
J. Biomol. Screen - vol. 12 521-535 (2007)

Publications
Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effects from chemical structure

ChemMedChem

Bender A, Scheiber J, Glick M, Davies JW, Azzaoui K, Hamon J, Urban L, Whitebread S, Jenkins JL
ChemMedChem - vol. 2 861-873 (2007)

Preclinical Safety Pharmacology (PSP) attempts to anticipate adverse drug reactions (ADRs) during early phases of drug discovery by testing compounds in simple, in vitro binding assays (that is, preclinical profiling). The selection of PSP targets is based largely on circumstantial evidence of their contribution to known clinical ADRs, inferred from findings in clinical trials, animal […]

Publications
A comparison of the chemical properties of drugs and FEMA/FDA notified GRAS chemical compounds used in the food industry

Food and Chemical Toxicology

Sprous DG, Salemme FR
Food and Chemical Toxicology - vol. 45 1419-1427 (2007)

The range of molecular properties of generally recognized as safe (GRAS) compounds that are typically used in food and beverage products is compared to marketed drugs. It is observed that GRAS compounds differ from marketed drugs with respect to several molecular descriptors, including molecular weight, H-bond acceptor count, H-bond donor count, aromatic ring count, basic […]

Publications
Structure of Saccharomyces cerevisiae Chitinase 1 and Screening-Based Discovery of Potent Inhibitors

Chemistry and Biology

Hurtado-Guerrero R, van Aalten DMF
Chemistry and Biology - vol. 14 589-599 (2007)

Chitinases hydrolyse the ??(1,4)-glycosidic bonds of chitin, an essential fungal cell wall component. Genetic data on a subclass of fungal family 18 chitinases have suggested a role in??cell wall morphology. Specific inhibitors of these enzymes would be useful as tools to study their role in cell wall morphogenesis and could possess antifungal properties. Here, we […]

Publications
Differentiating Alzheimer disease-associated aggregates with small molecules

Neurobiology of Disease

Honson NS, Johnson RL, Huang W, Inglese J, Austin CP, Kuret J
Neurobiology of Disease - vol. 28 251-260 (2007)

Alzheimer disease is diagnosed postmortem by the density and spatial distribution of β-amyloid plaques and tau-bearing neurofibrillary tangles. The major protein component of each lesion adopts cross-β-sheet conformation capable of binding small molecules with submicromolar affinity. In many cases, however, Alzheimer pathology overlaps with Lewy body disease, characterized by the accumulation of a third cross-β-sheet […]

Publications
Permeation of permanently positive charged molecules through artificial membranes-Influence of physico-chemical properties

European Journal of Pharmaceutical Sciences

Fischer H, Kansy M, Avdeef A, Senner F
European Journal of Pharmaceutical Sciences - vol. 31 32-42 (2007)

The aim of this study was to investigate the permeation properties of 20 permanently positive charged molecules in the parallel artificial membrane permeability assay (PAMPA). Eight of them were derivatives of the N-alkyl-isoquinolinium salt and 12 were congeners of the dye rhodamine 110. Five out of 12 molecules from the rhodamine 110 series have one […]

Publications
A high-throughput screen for aggregation-based inhibition in a large compound library

Journal of Medicinal Chemistry

Feng BY, Simeonov A, Jadhav A, Babaoglu K, Inglese J, Shoichet BK, Austin CP
Journal of Medicinal Chemistry - vol. 50 2385-2390 (2007)

High-throughput screening (HTS) is the primary technique for new lead identification in drug discovery and chemical biology. Unfortunately, it is susceptible to false-positive hits. One common mechanism for such false-positives is the congregation of organic molecules into colloidal aggregates, which nonspecifically inhibit enzymes. To both evaluate the feasibility of large-scale identification of aggregate-based inhibition and […]

Publications
Understanding false positives in reporter gene assays: In silico chemogenomics approaches to prioritize cell-based HTS data

Journal of Chemical Information and Modeling

Crisman TJ, Parker CN, Jenkins JL, Scheiber J, Thoma M, Kang ZB, Kim R, Bender A, Nettles JH, Davies JW, Glick M
Journal of Chemical Information and Modeling - vol. 47 1319-1327 (2007)

High throughput screening (HTS) data is often noisy, containing both false positives and negatives. Thus, careful triaging and prioritization of the primary hit list can save time and money by identifying potential false positives before incurring the expense of followup. Of particular concern are cell-based reporter gene assays (RGAs) where the number of hits may […]