MBT Domain Screening Service

MBT domains are specialized epigenetic reader modules that selectively recognize mono- and di-methylated lysine residues on histones, playing key roles in chromatin organization and transcriptional regulation. Their involvement in developmental processes and diseases such as cancer makes them promising yet challenging therapeutic targets. CD BioSciences offers expert MBT domain screening services to help researchers identify and characterize modulators of these important epigenetic readers.

Overview of MBT Domain

The MBT (malignant brain tumor) domain is a conserved protein module that functions as a reader of mono- and di-methylated lysine marks, particularly on histone tails (e.g., H3K9me1/2, H4K20me1/2). These domains are typically found in chromatin-associated proteins such as L3MBTL1, SFMBT1, and MBTD1, where they contribute to chromatin compaction, transcriptional repression, and the maintenance of cellular identity. Due to their shallow binding pockets and preference for lower methylation states, MBT domains present unique challenges for small-molecule inhibitor development. However, their critical roles in Polycomb repression complexes and links to oncogenic processes underscore their value as therapeutic targets. Systematic screening for MBT domain inhibitors is therefore essential for both probing their biological functions and developing potential epigenetic therapies.

Fig.1 (A) The H3K4-like methylation motifs in methylated proteins. (B) A model for the K42- and K117-methylation-dependent degradation of human SOX2 by L3MBTL3 and the CRL4-DCAF5 ubiquitin ligase complex. (Sun H, Zhang H., 2024)

Our Services

At CD BioSciences, we provide comprehensive MBT domain screening solutions designed to overcome the technical hurdles associated with these low-affinity reader domains. Leveraging sensitive detection technologies and deep expertise in methyl-lysine recognition biology, we deliver robust data to support hit identification, selectivity profiling, and functional validation for your research and drug discovery programs.

Customized Solution for MBT Domain Screening

CD BioSciences provides tailored screening solutions for MBT domain targets, employing high-sensitivity platforms such as AlphaScreen and TR-FRET to overcome the challenges of low-affinity interactions. Our approach enables precise identification of modulators targeting mono- and di-methyl-lysine recognition, supporting both mechanistic studies and early-stage drug discovery.

Target Coverage

1. Core MBT Family: L3MBTL1, L3MBTL3, L3MBTL4
2. Scaffold/Adaptor Proteins: SFMBT1, MBTD1
3. Custom Constructs: Client-provided MBT domains or engineered variants

Featured Analytical Services

1. Methylation-State Specificity Analysis: Differentiate compound activity against mono-methylated (me1) vs. di-methylated (me2) lysine recognition.
2. Cross-MBT Family Selectivity Profiling: Evaluate inhibitor selectivity across key MBT family members to ensure target specificity.
3. Structure-Activity Relationship (SAR) & Binding Mode Analysis: Provide insights into chemical determinants of activity and predict binding interactions to guide lead optimization.

Application Scenarios

1. Epigenetic Cancer Therapy Development: Screen for inhibitors targeting MBT proteins (e.g., SFMBT1 in prostate cancer) to intervene in pathological chromatin silencing.
2. Developmental Biology Research: Develop MBT‑specific chemical probes to elucidate their functional roles in embryonic development and cellular differentiation.
3. Multi‑Target Combination Strategy: Explore the synergistic potential of MBT inhibitors with other epigenetic drugs, such as EZH2 or BET inhibitors.
4. Translational Validation: Evaluate the functional efficacy of lead compounds in relevant disease models, including cancer cell lines and patient‑derived organoids.

Workflow of MBT Domain Screening Service

Our Advantages

1. Specialized Expertise in Low-Affinity Target Screening: We possess deep, proven experience in developing and optimizing highly sensitive assays specifically for challenging low-affinity interactions characteristic of MBT domains and other methyl-lysine readers.
2. Integrated Methyl-Lysine Reader Profiling Platform: Our service platform enables seamless selectivity profiling not only within the MBT family but also across other major methyl-lysine reader families (e.g., Chromodomains, Tudor domains), providing a comprehensive selectivity map for your compounds.
3. Tailored & Flexible Project Solutions: We offer fully customizable screening strategies, from fragment-based screening and natural product library analysis to focused lead optimization campaigns, designed to align precisely with your specific research stage and objectives.
4. End-to-End Quality Assurance & Expert Collaboration: Our workflow incorporates stringent controls and orthogonal validation at every step, ensuring data robustness, while our scientific team provides direct, collaborative partnership for strategic guidance throughout the project lifecycle.

While MBT domains represent a distinct class of methyl-lysine readers, CD BioSciences provides comprehensive screening services across all major epigenetic reader families—including bromodomains, chromodomains, Tudor domains, PHD fingers, and SRA domains—offering fully integrated and customizable solutions for your complete epigenetic drug discovery needs. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

Reference

1. Sun H, Zhang H. Lysine methylation-dependent proteolysis by the malignant brain tumor (MBT) domain proteins[J]. International Journal of Molecular Sciences, 2024, 25(4): 2248.