Multiple Domains Screening Service

Inquiry

Comprehensive understanding of compound selectivity across diverse epigenetic reader families is critical for effective drug discovery and mechanistic elucidation. CD BioSciences provides an integrated multiple domains screening service, enabling simultaneous profiling of key reader domains—such as bromodomains, chromodomains, tudor, MBT, PHD, and SRA domains—to deliver actionable insights into polypharmacology and off-target effects, accelerating your path from screening to validated leads.

Significance of Multiple Domains Screening

The functional diversity of epigenetic reader domains—such as bromodomains, chromodomains, Tudor, MBT, PHD, and SRA domains—lies in their specific recognition of distinct histone modifications and their cooperative roles within gene regulatory networks. In modern epigenetic drug discovery, there is a growing emphasis on compound selectivity and multi-target synergies, highlighting the limitations of single-domain screening approaches. Integrated multi-domain screening is therefore essential, as it enables the simultaneous assessment of compound activity across various reader families, facilitating selective optimization, multi-target pharmacology studies, and early-stage evaluation of potential off-target effects.

The input sequence is a multi-domain protein (or protein complex) sequence, which is segmented into single-domain sequences. The single-domain structures are generated by a single-domain structure predictor.

Fig.1 The input sequence is a multi-domain protein (or protein complex) sequence, which is segmented into single-domain sequences, and the single-domain structures are generated by a single-domain structure predictor. (Xia Y, et al., 2023)

Our Services

As a pioneer in epigenetic drug discovery services, CD BioSciences offers industry-leading integrated multi-domain screening solutions capable of simultaneously analyzing multiple epigenetic reader domains to comprehensively characterize compound selectivity. This approach accelerates the discovery of multi-target drugs and deepens our understanding of epigenetic regulatory mechanisms.

One-stop Solution for Multiple Domains Screening

At CD BioSciences, we provide a fully integrated, one-stop solution for comprehensive epigenetic reader domain screening. Our platform enables parallel profiling of compounds against multiple domains within a single, streamlined workflow. This approach not only delivers a holistic view of compound selectivity and polypharmacology but also significantly reduces project timelines by consolidating what would traditionally require multiple separate screening campaigns.

  1. Targeted Domain Types

We support both individual and combined screening for the six major classes of epigenetic reader domains:

Domain Types Function Representative Protein Targets
Bromodomain Recognizes acetylated lysine residues.
  1. BET Family: BRD2, BRD3, BRD4, BRDT
  2. Non-BET: CREBBP/p300, ATAD2, TRIM24, BAZ2B, BRD9, TAF1
Chromodomain Recognizes methylated lysine residues.
  1. Polycomb Group: CBX2, CBX4, CBX6, CBX7, CBX8
  2. Heterochromatin Protein 1: HP1α (CBX5), HP1β (CBX1), HP1γ (CBX3)
Tudor Domain Recognizes methylated lysine/arginine.
  1. Histone Modification Readers: JMJD2A (KDM4A), 53BP1, TDRD3
  2. Splicing Factors: SMN, SPF30
MBT Domain Recognizes mono-/dimethylated lysine.
  1. L3MBTL1, L3MBTL3, MBTD1, SFMBT1
PHD Finger Recognizes methylated lysine.
  1. Chromatin Regulators: BPTF, ING family proteins (ING1, ING2, ING4), MLL (KMT2A), JARID1A (KDM5A)
SRA Domain Recognizes methylated cytosine (in DNA).
  1. UHRF1, UHRF2

* Note: The table above lists the primary reader domains we focus on for screening. Please contact us if you are interested in screening services for other domains.

  1. Diverse Screening Services

Our multi-domain screening platform offers flexible and focused service models to meet diverse research objectives. Below are the three primary approaches we provide:

  1. Selectivity Profiling: Screen a single compound or a focused series against a customized panel of reader domains to generate a comprehensive selectivity heatmap, identifying off-target interactions and guiding SAR for specificity.
  2. Focused Multi-Target Screening: Conduct parallel screening against a curated set of domains within a specific biological pathway (e.g., all reader domains in the Polycomb complex) to identify compounds with desired polypharmacology or synergistic potential.
  3. Primary Library Screening: Perform high-throughput screening of large compound libraries against one or two high-priority reader domains to discover novel hits, with optional counter-screening against a selectivity panel to prioritize leads early.
  1. Core Technology Platform

Our screening strategies are powered by an integrated suite of validated and advanced technologies, ensuring robust, sensitive, and physiologically relevant data generation across diverse reader domains. Below are our key technology platforms:

Cutting-edge Technology Support

  1. High-Throughput Binding Assays: We utilize homogeneous, plate-based technologies such as time-resolved fluorescence resonance energy transfer (TR-FRET), AlphaScreen, and fluorescence polarization (FP) for efficient primary screening and competition studies.
  2. Biophysical Analysis for Validation: To confirm binding and characterize interactions, we employ surface plasmon resonance (SPR) and bio-layer interferometry (BLI) for precise measurement of binding affinity (Kd) and kinetics (kon/koff).
  3. Cellular & Functional Assays: For translational relevance, we offer epigenetic reporter gene assays and Cellular Target Engagement assays to validate inhibitor activity in a cellular context.

Workflow of Multiple Domains Screening Service

Our Advantages

  1. Comprehensive Reader Domain Coverage: We support screening across all six major epigenetic reader domain families, offering a truly integrated platform for multi-target discovery and selectivity profiling.
  2. Broad Applicability: Our flexible service models are widely applicable to diverse research stages, from initial chemical probe characterization and lead optimization to mechanistic polypharmacology studies and translational drug development.
  3. Integrated & Customized Workflow: We provide a seamless, end-to-end workflow that can be fully customized, from domain panel design and parallel assay development to advanced cross-domain data analysis and reporting.
  4. High-Quality Data & Expert Support: Our commitment to stringent quality controls and orthogonal validation ensures robust, reproducible data, complemented by direct consultation with our experienced scientific team for strategic project guidance.

CD BioSciences' multiple domains screening service offers a powerful and integrated approach to help you navigate the complexity of epigenetic reader biology. By enabling simultaneous profiling across key domain families, we deliver the comprehensive selectivity and polypharmacology data essential for modern drug discovery and mechanistic research. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

Reference

1. Xia Y, Zhao K, Liu D, et al. Multi-domain and complex protein structure prediction using inter-domain interactions from deep learning[J]. Communications Biology, 2023, 6(1): 1221.

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