DNA Damage/Repair Management
ChemDiv offers high throughput screening (HTS) service
DNA Damage/Repair Management research platform
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173 assays, 8 groups of targets based on the DNA damage/repair pathway are available
DNA Damage/Repair pathways: base excision repair (BER), direct reversal repair (DRR), DNA damage signaling (DDS), homologous recombination repair (HRR), mismatch repair (MMR), nonhomologous end-joining (NHEJ), nucleotide excision repair (NER), translesion synthesis (TLS)
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High content screening platform and 3 lead characterization methods: ELISA, flow cytometry, western blotting
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Track record of 25+ years’ experience, expertise in all major therapeutic areas
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Full discovery support of your projects
CADD, synthetic and medicinal chemistry, preclinical biology, animal studies, CMC and formulation
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Screening of up to 1.6M compounds
Cherry-pickable collection
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Support for compound selection
Custom selection and screening set preparation from 1.6M stock available compounds
More details on prices, time, or research specificity - please contact chemdiv@chemdiv.com
The crucial goal for targeting DNA damage/repair proteins is to diminish the survivability of the cancer cells. For instance, DNA-PKcs central role in the repair of double-stranded breaks in DNA makes this protein a perfect target for small molecule studies. Another example of such regulation is ATM and ATR catalytic activity inhibition by caffeine, which sensitizes tumor cells to ionizing radiation.
High-throughput screening systems allow the study of different aspects of DNA damage and repair management in cells. ChemDiv offers following assay platform:
High content (HC):
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The cellular model is exposed to the stimulus of interest
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The added fluorescent compounds interact with the histone marking damaged fragment of DNA
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Magnitude of the fluorescence is processed and analyzed by complex algorithms automatically
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The signal from the images of cells is recorded from all the wells of 384-well microplate
Figure 1. Schematic algorithm of the high content screening. The necessity of a stimulus of interest is to trigger DNA damage response pathways in cells.
ChemDiv also provides methods for the lead characterization, such as ELISA, flow cytometry and western blotting:
ELISA
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Numerous markers produced by cell based on how DNA was damaged serve as antigens for the studies
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The antigens are bound to the wells of a microplate
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Specific to the antigen antibodies, then reporter antibodies and coloring agents are added to tag the molecule of interest
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Change in color allows to indirectly measure the amount of damaged DNA
Flow cytometry
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A suspended sample of dye-loaded cells is arranged in a single line to pass through laser beam one by one
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Signal from passing cells is registered to count and characterize them
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Histone marking DNA damage is tagged by fluorescently labeled antibody
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Approximately 10000 cells can be analyzed in less than one minute
Western blotting
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Proteins are separated via the gel electrophoresis based on their molecular weight
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Polyvinylidene fluoride (PDVF) membrane produces a band for each of the proteins
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Incubation with specific antibodies leads to the localization of the protein of interest
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The thickness of the remaining band directly depends on the amount of protein present
List of targets: