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SMARCA2/4 Cell Panel Screening Service: Accelerate Your Precision Oncology Drug Discovery!
The SWI/SNF chromatin remodeling complex, with its catalytic subunits SMARCA2 (BRM) and SMARCA4 (BRG1), is a fundamental regulator of gene expression and chromatin dynamics. Mutations within SWI/SNF subunits are frequently observed across various human cancers, leading to unique dependencies on the remaining functional paralog. This vulnerability creates a powerful opportunity for synthetic lethality, where selective targeting of the essential SMARCA2/4 paralog can induce cancer cell death while sparing healthy cells. Recent research highlights the SMARCA2/4 ATPase domain as a promising therapeutic target, underscoring its crucial role in defined transcriptional programs, thereby supporting the credibility and importance of this screening approach.
Creative Biolabs' SMARCA2/4 cell panel screening service provides a robust and systematic approach to identify and validate compounds that exploit the synthetic lethality associated with SWI/SNF deficiencies. Clients can expect clear deliverables, including comprehensive data on compound efficacy, selectivity, and dose-response in a panel of well-characterized cancer cell lines. This service is designed to de-risk your early drug discovery efforts by pinpointing promising drug candidates that are highly potent and selective for cancers with specific SMARCA2/4 vulnerabilities. We provide actionable insights that guide lead optimization and accelerate your preclinical development.
Strategies for Targeting SMARCA2/4 in Cancer Therapy
Our approach to SMARCA2/4 cell panel screening is strategically designed to capitalize on the concept of synthetic lethality. We focus on identifying small molecules that selectively impair the viability of cancer cells harboring specific SWI/SNF complex alterations while sparing wild-type cells. This strategy includes:
Differential Sensitivity Profiling: Screening compounds across a panel that includes SMARCA2/4 mutant, knockdown, and wild-type cell lines to identify compounds exhibiting differential sensitivity.
Targeting the ATPase Domain: Leveraging insights into the therapeutic relevance of the SMARCA2/4 ATPase domain, our assays are designed to detect inhibitors that specifically interfere with the catalytic activity essential for chromatin remodeling.
High-Throughput and Phenotypic Screening: Combining rapid, high-throughput capabilities with phenotypic assays allows for efficient identification of compounds that disrupt cell growth and survival in relevant genetic backgrounds.
Customized Assay Design: Adapting screening parameters and cell models to address specific research questions, such as identifying compounds effective in particular cancer types (e.g., lung cancer, synovial sarcoma, rhabdoid tumors) where SWI/SNF mutations are prevalent.
Workflow: Unlocking Synthetic Lethality Through Comprehensive Screening
1. Cell Line Selection & Preparation
We identify and prepare a diverse panel of cancer cell lines, including those with defined SMARCA2/4 mutations (e.g., SMARCA4-deficient, SMARCA2-deficient, and wild-type controls) and other relevant epigenetic backgrounds. Cells are cultured under optimized conditions and plated in high-throughput formats.
2. Assay Development & Optimization
Robust cell viability or proliferation assays are established and optimized for high-throughput screening, ensuring sensitivity and reproducibility. This involves determining optimal cell density, incubation times, and detection methods (e.g., luminescence-based ATP quantification, fluorescent viability dyes).
3. Compound Treatment & Screening
Test compounds are precisely added to the prepared cell panels across a range of concentrations to generate dose-response curves. Primary screening can be performed at single or multiple concentrations to identify initial hits.
4. Data Acquisition & Analysis
High-quality data is acquired using automated plate readers and rigorous quality control measures. Raw data is then processed and analyzed to determine parameters such as IC50 values, maximum inhibition, and selectivity profiles. Statistical analysis identifies significant hits and potential synthetic lethal interactions.
5. Hit Validation & Mechanism Elucidation
Promising hits are subjected to secondary validation assays to confirm their activity and rule out false positives. This may include orthogonal assays, target engagement studies, or more in-depth cellular assays to begin elucidating the compound's precise mechanism of action within the SMARCA2/4 pathway.
Required Starting Materials: To initiate the service, clients typically need to provide:
Test Compounds: Compounds for screening, supplied in a suitable format (e.g., DMSO stock, specified concentration range).
Preliminary Target Data (Optional but Recommended): Any existing data regarding the compounds' known or predicted activity against SMARCA2/4 or related epigenetic targets.
Specific Research Objectives: Clear definition of desired outcomes, such as identifying pan-SMARCA2/4 inhibitors or compounds selective for specific mutation types.
What We Can Offer
Creative Biolabs offers a comprehensive suite of capabilities tailored for SMARCA2/4 Cell Panel Screening:
Extensive Cell Line Library: Access to a broad collection of well-characterized human cancer cell lines, including those with defined mutations or genetic modifications within the SMARCA2/4 and SWI/SNF pathways, and their wild-type counterparts.
Customizable Cell Panel Construction: Ability to construct bespoke cell panels based on specific client requirements, focusing on particular cancer types or genetic backgrounds relevant to your research.
High-Throughput Screening (HTS) Platforms: State-of-the-art automated HTS infrastructure enabling rapid and efficient screening of large compound libraries.
Diverse Readout Technologies: Expertise in various detection methods for cell viability and proliferation, including luminescence, fluorescence, and absorbance assays, ensuring optimal signal detection and data quality.
Expert Data Analysis and Interpretation: Our experienced scientists provide comprehensive data analysis, including IC50 determination, selectivity profiling, and insightful interpretations to guide your lead optimization efforts.
Flexible Study Designs: Tailored experimental designs, from primary screening to secondary validation and mechanistic studies, to meet the unique needs of your drug discovery program.
Highlights
Proven Track Record
Our extensive experience in drug discovery, combined with numerous successful collaborations and projects, demonstrates our capability to deliver high-quality, actionable results.
Integrated Solutions
We offer a seamless, end-to-end drug discovery platform, ensuring continuity and efficiency from target validation to preclinical candidate selection.
Cutting-Edge Technology
Investment in advanced instrumentation and methodologies guarantees the highest standards of data quality and throughput.
Client-Centric Approach
We prioritize understanding your specific challenges and objectives, offering flexible, customized solutions and proactive project management to ensure your success.
Customer Reviews
"Using Creative Biolabs' SMARCA2/4 cell panel screening service in our research has significantly improved our ability to identify novel synthetic lethal compounds. The detailed dose-response data across diverse cell lines allowed us to prioritize leads much faster than anticipated." – March 2024, Dr. A*n
"The precision of the SMARCA2/4 screening provided by Creative Biolabs was exceptional. We were particularly impressed with their expertise in assay optimization, which facilitated the rapid validation of our hit compounds and clarified their mechanism of action against SWI/SNF-mutant cells." – January 2025, J. M*r
"Creative Biolabs' SMARCA2/4 Cell Panel Service offered distinct advantages over in-house biochemical assays for our specific project, providing crucial cellular context. Their comprehensive data package helped us overcome initial challenges in compound selectivity, moving our epigenetic inhibitor program forward with confidence." – December 2024, K. F*g
FAQs
What types of compounds can be screened using this service?
We can screen a wide range of small molecules, including novel chemical entities, natural products, and existing compound libraries. Our platforms are adaptable to various compound types.
How many cell lines are included in the standard SMARCA2/4 cell panel?
Our standard panel includes a diverse set of cancer cell lines with characterized SMARCA2/4 statuses (mutant, wild-type, knockdown). We also offer customization to meet specific research needs.
What data will I receive from the screening?
You will receive comprehensive data, including raw readings, normalized data, dose-response curves, IC$_{50}$ values, and selectivity profiles for your compounds across the screened cell lines.
Can I provide my own cell lines for the screening?
Yes, absolutely. We welcome clients to provide their proprietary cell lines, which can be integrated into our screening platforms after our internal validation process.
How does this service help identify synthetic lethal interactions?
By comparing compound effects in cell lines with different SMARCA2/4 genetic backgrounds (e.g., wild-type vs. mutant), we can identify compounds that selectively kill or inhibit the growth of cells dependent on specific SMARCA2/4 paralogs.
Extended Services
To further support your drug discovery journey related to SMARCA2/4 and epigenetic targets, Creative Biolabs offers several complementary services:
Kinase Profiling: Comprehensive profiling of compounds against a vast panel of kinases to assess selectivity and identify potential off-target effects.
Targeted Protein Degradation Services: Explore the development of degraders targeting SMARCA2/4 or other proteins.
DNA Damage Response (DDR) Assays: Investigate compounds that modulate DDR pathways, which are often interconnected with epigenetic regulation and synthetic lethality.
In Vitro Safety Assessment: Detailed safety pharmacology profiling to predict potential adverse effects early in development.
In Vivo Oncology Models: Validate the efficacy and pharmacodynamics of your lead compounds in relevant preclinical animal models.
For detailed information on our SMARCA2/4 cell panel screening service or to discuss your specific project needs, please contact us at your early convenience.
