To prioritize compounds with a higher likelihood of success, artificial intelligence models can be used to predict absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of molecules quickly and efficiently. Models were trained with BioPrint database proprietary data along with public datasets to predict various ADMET end points for the SAFIRE platform. SAFIRE models performed at or above 75% accuracy and 0.
View Article and Find Full Text PDFJ Pharmacol Toxicol Methods
July 2019
Background: Several factors contribute to the development failure of novel pharmaceuticals, one of the most important being adverse effects in pre-clinical and clinical studies. Early identification of off-target compound activity can reduce safety-related attrition in development. In vitro profiling of drug candidates against a broad range of targets is an important part of the compound selection process.
View Article and Find Full Text PDFThe term 'pharmacological promiscuity' describes the activity of a single compound against multiple targets. When undesired, promiscuity is a major safety concern that needs to be detected as early as possible in the drug discovery process. The analysis of large datasets reveals that the majority of promiscuous compounds are characterized by recognizable molecular properties and structural motifs, the most important one being a basic center with a pK(a)(B)>6.
View Article and Find Full Text PDFWe previously devised cell-free conditions supporting efficient replication of bovine papillomavirus type 1 (BPV1) DNA (C. Bonne-Andréa, S. Santucci, and P.
View Article and Find Full Text PDFExtracts prepared from either mouse cells or monkey cells were examined for the ability to support in vitro bovine papillomavirus type 1 (BPV1) DNA replication, and they were used in parallel as a source of host replication proteins for affinity chromatography. DNA synthesis exhibited an absolute requirement for BPV1 E1 protein. In contrast to previous observations, we found that low levels of E1 were highly efficient in initiating DNA replication in the absence of the BPV1 transcription factor E2.
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