PROTAC BRD4 degrader-1 CAS 2743427-26-9 98% White to Off-White Solid PROTAC BRD4 Degrader for Epigenetic & Oncology Research

1. Product Overview

PROTAC BRD4 degrader-1 (CAS: 2743427-26-1) is a highly potent and selective bifunctional PROTAC (Proteolysis Targeting Chimera) designed for the targeted degradation of Bromodomain-containing protein 4 (BRD4). It recruits the Cereblon (CRBN) E3 ubiquitin ligase to facilitate the ubiquitination and subsequent proteasomal degradation of BRD4, a key epigenetic reader protein implicated in transcriptional regulation of oncogenes such as MYC. This compound represents a cutting-edge chemical biology tool for studying bromodomain inhibition via protein destruction rather than traditional occupancy-based blocking, making it indispensable for epigenetic and cancer research.

2. Key Features and Advantages

• Event-Driven Pharmacology: Unlike BET inhibitors that competitively block the acetyl-lysine binding pocket, this PROTAC induces complete removal of BRD4 from the cellular environment, leading to more profound and sustained suppression of target gene expression.

• High Potency & Selectivity: Demonstrates low DC₅₀ (half-maximal degrading concentration) in nano-molar range for BRD4 (BD1/BD2 domains), with significantly reduced activity against other bromodomain family members (BRD2/BRD3) at working concentrations.

• Cereblon (CRBN) Recruitment: Utilizes a optimized thalidomide-derived ligand to engage the CRBN E3 ligase, ensuring efficient ternary complex formation and robust ubiquitin transfer.

• Research-Grade Purity: Supplied at ≥98% purity (HPLC), validated by NMR and LC-MS, ensuring reproducibility in sensitive cell-based assays and Western blot analyses.

• Superior Phenotypic Impact: Exhibits stronger anti-proliferative effects in BRD4-dependent cancer cell lines (e.g., MV4-11, HL-60) compared to standard small-molecule BET inhibitors like JQ1.

3. Main Applications

• Epigenetics Research: Used to dissect the functional role of BRD4 in chromatin remodeling, super-enhancer maintenance, and transcriptional pause-release of oncogenic drivers.

• Oncology Drug Discovery: Serves as a lead compound or pharmacological probe in acute myeloid leukemia (AML), multiple myeloma, and triple-negative breast cancer models to evaluate degradation-based therapeutic strategies.

• Protein Degradation Studies: Ideal for establishing proof-of-concept in PROTAC mechanism validation, including ternary complex recruitment assays, ubiquitination tracking, and rescue experiments using proteasome inhibitors (e.g., MG-132).

• Cell Viability & Apoptosis Assays: Applied in MTT/CCK-8 assays and Annexin V/PI staining to quantify apoptosis induction specifically mediated by BRD4 depletion.

• In Vivo Xenograft Models: Formulated in appropriate vehicles (e.g., 5% DMSO/95% corn oil) for evaluating tumor growth inhibition and pharmacokinetic/pharmacodynamic (PK/PD) relationships in murine studies.

4. Technical Specifications

5. Storage and Handling

• Reconstitution Protocol: Allow the sealed vial to reach room temperature before opening to prevent moisture condensation. Centrifuge briefly to collect powder at the bottom. Dissolve in anhydrous DMSO to prepare a 10 mM stock solution. Sonication may be applied briefly if precipitation occurs.

• Aliquot Recommendation: To preserve activity, divide the DMSO stock into single-use aliquots (e.g., 10–50 µL) immediately after preparation. Store aliquots at -80°C in low-retention microcentrifuge tubes.

• Avoid Freeze-Thaw: Strictly avoid repeated freeze-thaw cycles, which can cause compound precipitation and potency loss. Thaw only the required aliquot on ice immediately before use.

• Powder Storage: Keep the original container tightly sealed with desiccant present. Store at -20°C in a dark, dry environment (relative humidity <40%). For long-term archiving (>1 year), consider storage under inert argon or nitrogen atmosphere.

• Handling Precautions: Use in a certified fume hood. Wear nitrile gloves, safety goggles, and a lab coat. Minimize light exposure during handling as PROTACs may exhibit photosensitivity.

6. Safety Overview

PROTAC BRD4 degrader-1 is intended exclusively for Laboratory Research Use Only (LRUO). It is not for human or veterinary diagnostic, therapeutic, or consumable use. Classified as a hazardous substance under laboratory conditions: may cause skin irritation (Category 2), eye irritation (Category 2), and respiratory tract irritation if inhaled as dust. In case of skin contact, wash thoroughly with soap and water. In case of eye contact, rinse cautiously with flowing water for at least 15 minutes and seek medical attention. Dispose of waste in accordance with institutional regulations for organic chemical solvents and halogenated compounds. Always consult the full Safety Data Sheet (SDS) prior to experimentation.

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