PHD Finger Screening Service

Inquiry

Plant homeodomain (PHD) fingers are zinc-finger epigenetic reader domains that recognize specific histone modifications, playing crucial roles in chromatin signaling, transcriptional regulation, and DNA damage repair. Their dysregulation is linked to cancers and developmental disorders. CD BioSciences offers expert PHD finger screening services to enable the discovery of selective inhibitors and chemical probes for this multifaceted reader family.

Introduction to PHD Finger

The PHD finger is a conserved Cys4-His-Cys3 zinc-binding domain found in numerous chromatin-associated proteins. It functions primarily as an epigenetic reader, with different PHD fingers exhibiting distinct binding specificities—some recognize methylated histone marks (e.g., H3K4me3 by ING family PHDs), while others bind unmodified residues or even non-histone proteins. These interactions are critical for recruiting chromatin remodelers, regulating gene expression, and maintaining genomic stability. Given their central roles in complexes such as MLL, NuRD, and TIP60, and their frequent alteration in diseases like leukemia and neurodevelopmental disorders, PHD fingers represent promising yet challenging therapeutic targets. High-quality screening is therefore essential to identify specific modulators that can disentangle their complex biology and validate their therapeutic potential.

Signaling pathways of some PHD finger proteins in plant flowering and pollen development.

Fig.1 The signal pathway of partial PHD finger proteins involved in plant flowering and pollen development. (Quan W, et al., 2023)

Our Services

Leveraging deep expertise in zinc-finger epigenetic reader domains, CD BioSciences delivers end-to-end PHD finger screening solutions designed to address the unique structural and functional diversity of this reader class. By combining sensitive biochemical assays, biophysical validation, and expert data analysis, we provide reliable and actionable data to accelerate your target validation, probe development, and early-stage drug discovery efforts.

Comprehensive Solution for PHD Finger Screening

At CD BioSciences, we provide a comprehensive and integrated platform specifically for PHD finger screening, offering extensive target coverage and tailored screening services to meet diverse research objectives. Our solution is designed to deliver both breadth and depth, enabling systematic exploration of this important epigenetic reader family.

Target Coverage

Methylation-State Readers: ING2, ING4, ING5 PHD fingers (H3K4me3 readers); BPTF PHD finger
Unmodified/Other State Readers: AIRE PHD1, DNMT3L PHD, RAG2 PHD
Multidomain Complex Proteins: MLL1 (KMT2A) PHD3, JADE1 PHD, TIP60 PHD
Custom Targets: Client-provided PHD finger constructs or disease-associated mutants

Specialized Screening Services

Methylation-State Dependency Analysis: Determines compound or target specificity for distinct histone lysine methylation states (me0/me1/me2/me3) to guide selective modulator development.
Zinc-Finger Structural Integrity Testing: Assesses compound effects on zinc-coordination stability to identify true binding inhibitors and exclude non-specific chelators.
Structure-Function Relationship Elucidation: Correlates chemical features of hits with biological activity using structural insights to rationally guide optimization of potency and selectivity.

Workflow of PHD Finger Screening Service

Steps	Description
Project Scoping and Target Characterization	We initiate with a detailed consultation to define the specific PHD finger target, its histone modification preference, and screening objectives. This phase includes bioinformatic analysis of target specificity and preliminary assessment of domain stability for assay design.
Assay Development and Zinc-Chelation Optimization	Our team develops a sensitive biochemical binding assay (typically TR-FRET or AlphaScreen) specifically optimized for zinc-coordinated PHD domains. This critical step includes buffer optimization to maintain structural integrity and validation of binding specificity using control peptides.
High-Throughput Screening and Primary Hit Identification	We execute the validated screening protocol against compound libraries, employing zinc-chelator controls to identify artifacts. Primary hits are identified based on statistical significance and confirmed through single-point retesting.
Comprehensive Hit Validation and Characterization	Validated hits undergo detailed dose-response analysis (IC₅₀ determination) followed by orthogonal testing including zinc-chelator interference assays, thermal shift analysis for target engagement, and counter-screening against related PHD domains.
Integrated Data Analysis and Structure-Activity Reporting	We provide a comprehensive analysis package including validated hit lists with chemical structures, detailed selectivity profiles across methylation states, structural modeling of binding interactions, and specific recommendations for hit-to-lead optimization based on PHD finger pharmacophore characteristics.

Application Scenarios

Oncology Drug Discovery: Screening for inhibitors targeting PHD fingers within critical chromatin regulator complexes such as MLL and TIP60 for cancer therapy development.
Autoimmunity & Immunotherapy Research: Developing modulators of AIRE PHD1 to regulate autoimmune gene expression and advance novel immunotherapy approaches.
Chemical Probe Development: Creating selective PHD finger probes for fundamental chromatin biology studies and epigenetic target validation.
Polypharmacology & Combination Therapy Studies: Exploring synergistic effects of PHD finger inhibitors with other epigenetic drugs (e.g., BET or HDAC inhibitors) for enhanced therapeutic strategies.

Our Advantages

Deep Expertise in Zinc-Finger Reader Biology: Specialized knowledge in expressing, stabilizing, and assaying structurally sensitive PHD finger domains.
Integrated Reader Family Profiling: Ability to contextualize PHD finger data within broader epigenetic selectivity panels (e.g., Bromodomains, Chromodomains).
Tailored & Flexible Solutions: Customizable screening strategies from fragment libraries to focused lead optimization series.
End-to-End Quality & Collaboration: Rigorous assay controls, orthogonal validation, and direct scientific partnership throughout the project lifecycle.

Beyond PHD fingers, CD BioSciences offers comprehensive epigenetic reader screening services for all major domain families, including bromodomains, chromodomains, Tudor domains, MBT domains, and SRA domains, as well as integrated multiple domains screening. Our fully customizable platform supports every stage of your epigenetic drug discovery journey. Contact us today to discuss how we can tailor our services to your specific research objectives.

Reference

1. Quan W, Chan Z, Wei P, et al. PHD finger proteins function in plant development and abiotic stress responses: an overview[J]. Frontiers in Plant Science, 2023, 14: 1297607.