Identification of a Small Molecule Inhibitor of RAD52 by Structure-Based Selection.

It has been reported that inhibition of RAD52 either by specific shRNA or a small peptide aptamer induced synthetic lethality in tumor cell lines carrying BRCA1 and BRCA2 inactivating mutations. Molecular docking was used to screen two chemical libraries: 1) 1,217 FDA approved drugs, and 2) 139,735 drug-like compounds to identify candidates for interacting with DNA binding domain of human RAD52. Thirty six lead candidate compounds were identified that were predicted to interfere with RAD52 -DNA binding.

Evaluation of cancer dependence and druggability of PRP4 kinase using cellular, biochemical, and structural approaches.

PRP4 kinase is known for its roles in regulating pre-mRNA splicing and beyond. Therefore, a wider spectrum of PRP4 kinase substrates could be expected. The role of PRP4 kinase in cancer is also yet to be fully elucidated.

Personalized synthetic lethality induced by targeting RAD52 in leukemias identified by gene mutation and expression profile.

Homologous recombination repair (HRR) protects cells from the lethal effect of spontaneous and therapy-induced DNA double-stand breaks. HRR usually depends on BRCA1/2-RAD51, and RAD52-RAD51 serves as back-up. To target HRR in tumor cells, a phenomenon called "synthetic lethality" was applied, which relies on the addiction of cancer cells to a single DNA repair pathway, whereas normal cells operate 2 or more mechanisms.

Reproducibility of placental volume and vasculature indices obtained by 3-dimensional power Doppler sonography.

Objective: The purpose of this study was to evaluate the reproducibility of 3-dimensional (3D) power Doppler assessment of placental volumes and vascularization before adopting these in routine evaluation of normal and complicated pregnancies.

Methods: A prospective study was performed on 30 normal singleton pregnancies from 11 to 14 weeks. To evaluate placental vascularization, 3D power Doppler sonography was applied to obtain a placental volume, and the volume acquired was analyzed using virtual organ computer-aided analysis.

Does the combination of fronto-maxillary facial angle and nasal bone evaluation improve the detection of Down syndrome in the second trimester?

Objective: To determine if the combination of fronto-maxillary facial (FMF) angle and nasal bone (NB) evaluation improves the detection of Down syndrome (DS) in the second trimester.

Study Design: We compared the FMF angle measurements in euploid and DS fetuses seen between 2005 and 2008. The FMF angles were measured from stored two-dimensional (2-D) images by investigators blinded to the DS status of the fetus.

Molecular-modeling based design, synthesis, and activity of substituted piperidines as gamma-secretase inhibitors.

Alzheimer's disease (AD) is a debilitating disease widely thought to be associated with the accumulation of beta amyloid (Abeta) in the brain. Inhibition of gamma-secretase, one of the enzymes responsible for Abeta production, may be a useful strategy for the treatment of AD. Described below is a series of gamma-secretase inhibitors designed from a scaffold identified by a ROCS [J.