IntroductionStrategiesWorkflowWhat We Can OfferWhy Choose UsCustomer ReviewsFAQsExtended Services
DNA Damage Response (DDR) Targeting Assay Service: Accelerate Your Precision Oncology Pipeline!
The DDR is intrinsically linked to genotoxicity, the ability of chemical agents or physical stressors to cause damage to cellular DNA. Understanding genotoxicity is crucial for drug safety assessment, environmental risk evaluation, and identifying potential carcinogens. Creative Biolabs offers comprehensive genotoxicity assessment services, providing a critical safety and mechanistic understanding for your compounds and products. Our genotoxicity assessment services are designed to detect various types of DNA damage and chromosomal aberrations, ensuring compliance with regulatory guidelines and minimizing late-stage failures in development. We provide:
Bacterial Reverse Mutation Test (Ames Test): A foundational in vitro assay for detecting gene mutations.
In Vitro Mammalian Cell Micronucleus Test: Evaluates chromosomal damage and aneugenicity in mammalian cells.
In Vitro Chromosomal Aberration Test: Detects structural and numerical chromosomal abnormalities in cultured mammalian cells.
Comet Assay (Single Cell Gel Electrophoresis): A sensitive method for detecting and quantifying DNA strand breaks in individual cells.
DDR Pathway Analysis: While our DDR targeting assay service focuses on inhibiting DDR for therapeutic purposes, our broader genotoxicity assessment includes evaluating the integrity and function of these pathways in response to various agents. This helps determine if a compound is inducing DNA damage that overwhelms or compromises the cell's natural repair mechanisms.
Oxidative Stress Assays: Measurement of reactive oxygen species (ROS) and assessment of oxidative DNA damage, a common form of genotoxicity.
By integrating these services, we provide a holistic view of your compound's genotoxic potential, from basic mutagenicity screening to detailed mechanistic insights into how a compound interacts with cellular DNA and its repair machinery. The DDR is a fundamental cellular process maintaining genomic integrity, acting as a guardian against mutations and disease. Dysregulation of DDR pathways is a hallmark of cancer, presenting unique therapeutic vulnerabilities. At Creative Biolabs, DDR targeting assay service harnesses this critical biological understanding to offer specialized, high-precision assays designed to identify and characterize novel inhibitors of key DDR proteins, accelerating the development of targeted oncology therapies.
Strategies of this Service
Our DDR targeting assay service employs a multifaceted strategic approach to maximize the probability of identifying effective and selective therapeutic candidates:
Synthetic Lethality Exploitation: We strategically focus on DDR targets that, when inhibited, create a synthetic lethal interaction with pre-existing defects in cancer cells (e.g., targeting PARP in BRCA-deficient tumors). This approach minimizes toxicity to healthy cells while maximizing efficacy against cancer.
Broad Kinase Inhibition & Selectivity: Recognizing the central role of kinases in DDR signaling, our strategy includes comprehensive screening against a wide array of DDR-related kinases. We emphasize detailed selectivity profiling to identify compounds with optimal target specificity, mitigating off-target effects and potential toxicity.
Integrated Biochemical and Cell-Based Assays: Our approach integrates high-fidelity biochemical assays for direct enzyme inhibition with physiologically relevant cell-based assays. This ensures that hits identified in vitro demonstrate activity in a complex cellular environment, providing a more predictive pipeline for in vivo efficacy.
Mechanism of Action Elucidation: Beyond simple hit identification, our service is geared towards understanding the precise mechanism by which compounds exert their effects. This involves comprehensive analysis of cellular endpoints such as DNA damage markers (γH2AX), cell cycle progression, and apoptosis, providing crucial insights for lead optimization and drug development.
Biomarker Identification & Validation: We incorporate strategies for the identification and validation of predictive biomarkers. This enables patient stratification for future clinical trials, ensuring that the right drug reaches the right patient for personalized oncology.
Workflow
Required Starting Materials: To initiate your DDR targeting assay project, we typically require:
Target Protein/Gene Details: Information on the specific DDR target(s) of interest, including sequence information, known inhibitors, or assay considerations.
Compound Library: If applicable, details of your compound library (structure, quantity, solubility) for screening purposes.
Specific Research Questions: A clear articulation of your scientific hypotheses or the desired outcome of the assay service
What We Can Offer
Creative Biolabs provides a comprehensive suite of capabilities tailored for DDR drug discovery, offering flexibility to address diverse project requirements:
High-Throughput Screening (HTS) for DDR Targets: Rapid and efficient screening of large compound libraries against key DDR enzymes (e.g., PARP1/2, ATR, ATM, DNA-PK, CHK1/2, WEE1).
Precise IC50/EC50 Determination: Accurate quantification of compound potency in both biochemical and cellular contexts.
Extensive Selectivity Profiling: Screening against our comprehensive panel of over 400 human kinases to assess compound specificity and potential off-target effects crucial for drug safety.
Cellular Proliferation & Viability Assays: Assessment of compound impact on cancer cell growth and survival across various cell lines, including those with defined DDR deficiencies.
Apoptosis and Cell Cycle Analysis: Detailed analysis of programmed cell death induction and cell cycle arrest using flow cytometry and other advanced techniques.
Advanced Target Engagement Assays: Live-cell, proximity-based assays to directly measure compound binding to the DDR target within an intact cellular environment, confirming on-target activity.
DNA Damage Biomarker Analysis: Quantification of key DNA damage markers like γH2AX foci formation, validating the cellular induction of DNA damage by your compounds using immunofluorescence, western blot, and flow cytometry.
Robust Preclinical In Vivo Validation: Leveraging our capabilities in xenograft and patient-derived xenograft (PDX) models to assess drug efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) in a translational setting.
Expert Bioinformatics and Data Analysis: Comprehensive support for robust data interpretation, helping you derive meaningful insights from complex experimental results and inform subsequent discovery phases.
Why Choose Us?
Unrivaled Expertise: Our team comprises seasoned biologists, biochemists, and pharmacologists with over 20 years of collective experience in DDR biology and oncology drug discovery, ensuring sophisticated experimental design and insightful data interpretation.
Comprehensive Platforms: We offer an integrated suite of services, from high-throughput biochemical screening to advanced cellular and in vivo validation, covering the entire DDR drug discovery pipeline under one roof.
Cutting-Edge Technology: Continuous investment in state-of-the-art instrumentation and proprietary assay methodologies, including advanced target engagement platforms, provides you with the most accurate and reliable data.
Uncompromising Quality: Strict adherence to rigorous quality control protocols and robust data analysis ensures the highest levels of accuracy, reproducibility, and reliability for every project.
Customization and Flexibility: We recognize that every project is unique. Our services are highly customizable, offering bespoke solutions that precisely align with your specific research needs and timelines.
Accelerated Innovation: By streamlining complex research processes and providing actionable insights, we empower our partners to significantly accelerate their drug discovery programs, bringing life-saving therapies to patients faster.
Customer Reviews
[Exceptional Selectivity Profiling] "Using DDR targeting assay service at Creative Biolabs in our research has significantly improved the selectivity profiling of our novel PARP inhibitors, giving us confidence in their off-target potential compared to previous methods. The detailed report allowed us to quickly down-select our lead compounds, saving valuable resources." – 3 Months Ago, Dav*** S.
[Accelerated Target Validation] "Rapid and high-quality DDR assays at Creative Biolabs have facilitated our target validation efforts for ATM inhibitors, allowing us to pivot quickly and efficiently. The clear readouts for both biochemical potency and cellular impact were crucial for our early-stage decision-making." – 6 Months Ago, Jih*** L.
[Precise Mechanism of Action] "Their comprehensive cellular functional assays and γH2AX analysis provided precise insights into the mechanism of action of our CHK1 inhibitors, invaluable for our lead optimization. The data was far more robust than what we could generate in-house with limited resources." – 1 Month Ago, Kat*** R.
FAQs
What types of DDR targets can you screen for?
We offer screening for a broad spectrum of DDR targets, including but not limited to PARP1/2, ATR, ATM, DNA-PK, CHK1/2, WEE1, MRE11, CDK, TOP1/2, AURKA/B, and PLK1. If your target isn't listed, please inquire, as our capabilities are constantly expanding.
Do you provide both biochemical and cell-based assays?
Yes, absolutely. Our service integrates both high-fidelity biochemical assays for direct enzyme activity measurement and robust cell-based assays to evaluate compound efficacy and mechanism of action in a physiologically relevant cellular context.
How do you ensure the quality and reproducibility of your assay data?
Quality and reproducibility are paramount at Creative Biolabs. We employ rigorous quality control measures, including strict SOPs, extensive assay validation, use of positive and negative controls, and redundant testing. Our state-of-the-art equipment is regularly calibrated to ensure consistent, high-quality results.
How do you identify and characterize hits from a screen?
After initial screening, potential hits undergo rigorous re-confirmation. We then perform dose-response curves to determine IC50/EC50 values and conduct selectivity profiling. Further characterization can include target engagement assays and DNA damage biomarker analysis to understand the compound's mechanism.
Can you assess the mechanism of action of our compounds?
Definitely. Beyond identifying hits, we offer a suite of cellular functional assays, including cell cycle analysis, apoptosis assays, and specific DNA damage marker quantification (e.g., γH2AX foci), to provide deep insights into your compounds' mechanism of action.
Do you offer in vivo validation for DDR inhibitors?
Yes, our comprehensive platform includes robust preclinical in vivo models, such as xenografts and patient-derived xenografts (PDX), to assess the efficacy, pharmacokinetics, and pharmacodynamics of your DDR inhibitors in a translational setting.
How does your service compare to in-house assay development?
Creative Biolabs offers significant advantages over in-house development, including access to a vast panel of DDR targets and kinases, cutting-edge instrumentation, specialized expertise, and established, validated workflows. This translates to faster turnaround times, higher data quality, and reduced operational costs for your team.
Extended Services
Creative Biolabs is your integrated partner for drug discovery, offering a range of complementary services that can further accelerate your oncology pipeline beyond the DDR targeting assay service:
Kinase Profiling Services: Beyond DDR targets, leverage our extensive kinase panel screening for broader drug discovery and selectivity assessment.
Cell Line Development: Custom generation of stable cell lines with specific genetic modifications or reporter constructs for specialized assay needs.
Custom Assay Development: Expertise in developing bespoke biochemical and cell-based assays for novel targets or unique experimental setups.
Compound Library Screening: Comprehensive high-throughput screening services for diverse therapeutic areas and target classes.
Preclinical In Vivo Oncology Services: From xenograft models to complex PDX studies, we provide robust in vivo efficacy and pharmacokinetic/pharmacodynamic assessments.
Bioanalytical Services: Expertise in ADME/PK studies to support the preclinical development of your drug candidates.
At Creative Biolabs, we are committed to unlocking the full therapeutic potential of DDR targeting. Our specialized DDR targeting assay service, backed by two decades of expertise, cutting-edge technology, and a client-centric approach, is designed to accelerate your drug discovery programs. We provide the precise, reliable data and insightful analysis you need to identify promising candidates, validate their mechanisms, and move closer to delivering life-changing therapies to patients. Partner with us to streamline your research and achieve your oncology goals with unparalleled efficiency.
Ready to advance your DDR drug discovery project? Our team of expert scientists is available to discuss your specific needs, answer your questions, and design a customized service package. Contact Our Team for More Information and to Discuss Your Project!
