DBR4 Antibody

BRD4 Antibody Overview

BRD4 antibodies are immunological tools designed to detect and study BRD4, a member of the BET (Bromodomain and Extra-Terminal) protein family. BRD4 binds acetylated lysine residues on histones via its bromodomains, facilitating the recruitment of transcriptional machinery to super-enhancers and regulating oncogene expression (e.g., MYC, BCL2) .

Validated BRD4 Antibodies

Two widely cited BRD4 antibodies include:

3.1. Super-Enhancer and Oncogene Regulation

BRD4 antibodies have been instrumental in identifying BRD4’s dual role in transcription:

• Activation: BRD4 recruits P-TEFb to phosphorylate RNA Pol II, driving oncogene expression (e.g., MYC) .

• Repression: BRD4 interacts with LSD1/NuRD complexes to silence drug-resistance genes (e.g., GNA13, PDPK1) .

Example: ChIP-seq using ab128874 revealed BRD4 occupancy at super-enhancers of MYC in lymphoma, which is disrupted by JQ1 inhibitors .

3.2. Therapeutic Development

BRD4 inhibitors (e.g., JQ1, AZD5153) synergize with antibodies to study resistance mechanisms:

• Prolonged BRD4 inhibition destabilizes LSD1, upregulating drug-efflux genes (e.g., ABCG2) .

• PROTAC degraders (e.g., dBET6) coupled with antibodies enhance tumor suppression in preclinical models .

Clinical Relevance

BRD4 antibodies are critical for:

1. Biomarker Validation: Detecting BRD4 overexpression in breast cancer, gliomas, and hematologic malignancies .

2. Drug Monitoring: Quantifying target engagement of BRD4 inhibitors via downstream gene modulation (e.g., HEXIM1, CD274) .

3. Immune Profiling: BRD4-linked immune evasion mechanisms (e.g., IgG4 interference in antibody-dependent cytotoxicity) .

Technical Considerations

• Recombinant vs. Traditional Antibodies: Recombinant formats (e.g., ab128874) show superior batch consistency and affinity (KD 10⁻¹¹–10⁻¹² M) .

• Cross-Reactivity: Antibodies may detect BRD2/3 due to bromodomain homology; KO validation is essential .

Future Directions

1. Dual-Targeting Antibodies: Combining BRD4 and PELI1 inhibitors to overcome chemoresistance .

2. ADC Development: Antibody-drug conjugates (ADCs) delivering BRD4 degraders (e.g., AZD5153) show promise in prostate cancer .