These results suggest that RD1504 is the best Th1-stimulating antigen
present in RD15, and therefore may be a potential vaccine candidate against TB.”
“Kinases AG-881 solubility dmso are heavily pursued pharmaceutical targets because of their mechanistic role in many diseases. Small molecule kinase inhibitors (SMKIs) are a compound class that includes marketed drugs and compounds in various stages of drug development. While effective, many SMKIs have been associated with toxicity including chromosomal damage. Screening for kinase-mediated toxicity as early as possible is crucial, as is a better understanding of how off-target kinase inhibition may give rise to chromosomal damage. To that end, we employed a competitive binding assay and an analytical method to predict the toxicity of SMKIs. Specifically, we developed a model based on the binding affinity of SMKIs to a panel of kinases to predict whether a compound tests positive for chromosome damage. As training data, we used the binding affinity of 113 SMKIs against a representative subset of all kinases (290 kinases), yielding a 1136290 data matrix. Additionally,
these 113 SMKIs were tested for genotoxicity in an in vitro micronucleus test (MNT). Among a variety of models from our analytical toolbox, we selected using cross-validation a combination of feature selection and pattern recognition techniques: Kolmogorov-Smirnov/T-test hybrid as a univariate filter, followed by Random Forests for feature selection and Support Vector Machines (SVM) for pattern recognition. Feature selection identified 21 kinases predictive
of MNT. Using see more the corresponding binding affinities, the SVM could accurately predict MNT results AICAR in vivo with 85% accuracy (68% sensitivity, 91% specificity). This indicates that kinase inhibition profiles are predictive of SMKI genotoxicity. While in vitro testing is required for regulatory review, our analysis identified a fast and cost-efficient method for screening out compounds earlier in drug development. Equally important, by identifying a panel of kinases predictive of genotoxicity, we provide medicinal chemists a set of kinases to avoid when designing compounds, thereby providing a basis for rational drug design away from genotoxicity.”
“Thymofibrolipoma is an extremely rare tumor in the anterior mediastinum, and represents a histologic variant of the usual thymolipoma. Herein, we report a case of thymofibrolipoma in a 9-year-old girl who had a huge mass with fatty attenuation in the right hemithorax on chest computed tomography. She denied any subjective symptoms except mild fever. The surgically resected tumor was ovoid, soft and well-encapsulated, measuring 9.0 x 7.5 x 7.0 cm. The cut surface was light tan in color with yellowish streaks. Microscopically, two distinct areas were admixed in different proportions.