We measured the « druggability » of the ATP-dependent luciferase derived from the firefly Photuris pennsylvanica that was optimized using directed evolution (Ultra-Glo, Promega). Quantitative high-throughput screening (qHTS) was used to determine IC(50)s of 198899 samples against a formulation of Ultra-Glo luciferase (Kinase-Glo). We found that only 0.1% of the Kinase-Glo inhibitors showed an IC(50) < 10 […]

We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT(2C) agonist, a series of 1-aminomethyl-2-phenylcyclopropanes was investigated as 5-HT(2C) agonists through iterative structural modifications. […]

Understanding how survival is regulated in human embryonic stem cells (hESCs) could improve expansion of stem cells for production of cells for regenerative therapy. There is great variability in comparing the differentiation potential of multiple hESC lines. One reason for this is poor survival upon dissociation, which limits selection of homogeneous populations of cells. Understanding […]

A combined strategy based on the development of pharmacophore hypotheses and NMR approaches is reported for the identification of novel inhibitors of heparanase, a key enzyme involved in tumor metastasis through the remodeling of the subepithelial and subendothelial basement membranes, resulting in the dissemination of metastatic cancer cells. Several pharmacophore hypotheses were initially developed from […]

Computer-aided prediction of rodent carcinogenicity for the external test set consisting of 293 chemicals was performed by PASS (Prediction of Activity Spectra for Substances) and by CISOC-PSCT. The set included 64 carcinogens from ISS Carcinogens Data Bank and 229 noncarcinogens from the Prestwick Chemical Library. We calculated the accuracy of carcinogenicity prediction by PASS and […]