A5026683078- DNA Repair Mechanisms
- Carcinogens and Genotoxicity Assessment
- Molecular Biology Techniques and Applications
- Crystallography and molecular interactions
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Cell Image Analysis Techniques
- Synthetic Organic Chemistry Methods
- Cancer Treatment and Pharmacology
- DNA and Nucleic Acid Chemistry
- Pluripotent Stem Cells Research
- Genetically Modified Organisms Research
- Marine Sponges and Natural Products
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Plant-based Medicinal Research
- Microbial Natural Products and Biosynthesis
- Microtubule and mitosis dynamics
- PARP inhibition in cancer therapy
- Advancements in Semiconductor Devices and Circuit Design
- Genomics and Chromatin Dynamics
- Biopolymer Synthesis and Applications
Pfizer (United States)
2004-2024
It was by way of total synthesis that the issues concerning stereostructure leiodermatolide (1) have recently been solved; with target now being unambiguously defined, mission changes as to secure a meaningful supply this exceedingly scarce natural product derived from deep-sea sponge. To end, scalable route 19 steps (longest linear sequence) has developed, which features catalytic asymmetric propargylation highly enolizable β-keto-lactone, ring closing alkyne metathesis and modified Stille...
Aneuploidy is a major cause of human reproductive failure and plays large role in cancer. Phenolphthalein (PHT) induces tumors rodents but its primary mechanism does not seem to be DNA damage. In heterozygous TSG‐ p53 ® mice, PHT lymphomas also micronuclei (MN), many containing kinetochores (K), implying chromosome loss (aneuploidy). The induction aneuploidy would compatible with the normal gene seen lymphomas. this study, we confirm PHT's aneugenicity determine aneugenic by combining...
Abstract Genotoxicity testing guidelines require the assessment of clastogenic and aneugenic potential compounds. While in vitro micronucleus assays detect both types endpoints, it requires labor‐intensive microscopic scoring does not discriminate between two modes actions. Here, we present a novel high‐content imaging platform A375 human cells that addresses need for rapid while providing additional mechanistic information. We evaluated new with 12 compounds, three compounds from each class...
Abstract Risk management of in vitro aneugens for topically applied compounds is not clearly defined because there no validated methodology to accurately measure compound concentration proliferating stratum basale keratinocytes the skin. Here, we experimentally tested several known EpiDerm reconstructed human skin micronucleus assay and compared results flow cytometric mechanistic biomarkers (phospho-H3; MPM2, DNA content). We then evaluated similar (Ki-67, nuclear area) using...
Abstract Previously, we introduced an alternative adherent A375 cell line for clastogenicity and aneugenicity testing using a high content imaging platform. To further characterize the performance of cells, investigated sensitivity specificity TK6 cells by directly comparing micronucleus (MN) induction, cytotoxicity (relative counts, viability, apoptosis), (γH2AX), aneuploidy markers (pH 3, MPM‐2, polyploidy) flow cytometric methods. We evaluated 14 compounds across different mechanisms...
Poly(ADP-ribose) polymerase inhibitors (PARPi) are approved as monotherapies in BRCA1/2-mutated (m BRCA1/2) metastatic breast and ovarian cancers, advanced pancreatic castration-resistant prostate cancers. Differential safety profiles across PARPi necessitate improved mechanistic understanding of inhibitor differences, especially with expansion indications drug combinations. Here, we report vitro evaluations (–/+ PARP trapper temozolomide, TMZ) reference to total clinical mean concentration...