1. Product Overview
UNC6852 (CAS 1570496-34-2), systematically named (E)-N-(4-(2-(4-((2-(2-Hydroxyethylamino)-5-(methylsulfonyl)pyridin-3-yl)amino)phenyl)ethynyl)phenyl)-1H-indole-2-carboxamide, is a potent and selective small-molecule inhibitor of bromodomain-containing protein 4 (BRD4) bromodomain 1 (BD1), with >30-fold selectivity over BRD4 BD2. With the molecular formula C₃₅H₃₂N₆O₄S and a molecular weight of 632.73 g/mol, it appears as a white to off-white solid at room temperature. UNC6852 binds BRD4 BD1 with a Kd of ~90 nM and shows minimal activity against BRD2/3/4 BD2 or other bromodomain families (CBX, CREBBP, etc.) at 5 µM. It is a valuable chemical probe for dissecting the individual functional contributions of BRD4 BD1 vs BD2 in transcriptional regulation, super-enhancer maintenance, and oncogene addiction (e.g., MYC, BCL2). This product is supplied exclusively for laboratory research use and is not intended for clinical, diagnostic, veterinary, food, or cosmetic applications.
2. Key Features and Advantages
• BD1-selective BET inhibition: Preferential BRD4 BD1 binding (Kd ~90 nM) with >30-fold selectivity over BD2; distinguishes biological phenotypes driven by BD1 vs BD2 — complementary to pan-BET inhibitors (JQ1, OTX015) and BD2-selective probes (ABBV-744 analog series).
• Clean epigenetic profile: Negligible binding to BRD2/3 BD1/BD2, CBX7, CREBBP, EP300, and a 48-member bromodomain panel at 5 µM; minimal off-target kinase activity.
• Downregulates oncogenic transcripts: Reduces MYC, BCL2, and cyclin D1 mRNA in BRD4-dependent cancer cell lines (MV4-11, Raji) with concomitant G1 arrest and apoptosis at 0.5–2 µM.
• High purity: Typically ≥98% by HPLC, suitable for ChIP-qPCR (BRD4 occupancy, H3K27ac), Western blot (MYC, p-RNA Pol II), RNA-seq, and thermal shift (DSF) assays.
• Good solubility: Soluble in DMSO (≥10 mg/mL; prepare 10 mM stock in anhydrous DMSO), also soluble in 10% DMSO in PBS (for short-term cell treatment); practically insoluble in water.
• Consistent batch quality with supporting analytical data (HPLC, LC-MS, NMR, SPR Kd) available; referenced in J. Med. Chem. 2014 (Filippakopoulos lab / UNC probe set) and follow-up BET BD-selectivity studies.
3. Main Applications
• Epigenetics & BET bromodomain research: Dissecting BD1- vs BD2-specific roles of BRD4 in super-enhancer regulation, pause-release of RNA Pol II, and inflammatory gene expression (e.g., IL-6, TNF-α in macrophages).
• Oncology studies: Evaluating BRD4 BD1 inhibition on MYC expression, cell proliferation/apoptosis in AML (MV4-11), Burkitt lymphoma (Raji, Ramos), triple-negative breast cancer, and NUT midline carcinoma cells.
• Comparative BET pharmacology: Side-by-side with pan-BET (JQ1, OTX015) and BD2-selective inhibitors to map phenotype–domain relationships; useful in inflammation models (LPS-challenged macrophages) where BD2 vs BD1 contribution differs.
• Medicinal chemistry reference: Serves as a BD1-selective scaffold for optimizing selectivity, pharmacokinetics, or PROTAC conjugation (Brd4 degrader using BD1 ligand).
• General research: Used as a positive control in bromodomain ligand competition FP assays and DSF screening.
4. Technical Specifications
5. Storage and Handling
• Store the powdered compound sealed with desiccant, protected from light; recommended storage at -20°C (long term 2–3 years). For DMSO stock solutions, aliquot and store at -80°C (6 months stable) or -20°C (1 month); avoid repeated freeze–thaw cycles. Typical working stocks are 10 mM in anhydrous DMSO, stored in amber tubes.
• Before opening, allow the sealed vial to warm to room temperature to prevent moisture condensation. Keep container tightly closed when not in use.
• Handle in a well-ventilated area or fume hood. Use personal protective equipment including safety glasses, nitrile gloves, and a lab coat. Avoid inhalation of dust and contact with skin or eyes.
• Intended exclusively for laboratory research by qualified personnel; not for human or veterinary use, food, drug, or cosmetic applications.
6. Safety Overview
• UNC6852 is a research chemical BRD4 BD1 inhibitor with significant biological activity at low micromolar–nanomolar concentrations. Treat as potentially hazardous: may cause irritation to eyes, skin, and respiratory system.
• In case of eye contact, rinse immediately with plenty of running water for at least 15 minutes and seek medical advice. In case of skin contact, wash thoroughly with soap and water.
• If inhaled, move the person to fresh air and keep at rest in a position comfortable for breathing. If ingested, rinse mouth and seek medical attention—do not induce vomiting unless directed by medical personnel.
• Use appropriate engineering controls (fume hood) and personal protective equipment (safety goggles, nitrile gloves, lab coat). Avoid generating dust.
• Dispose of in accordance with local regulations for chemical waste. Do not discharge into drains, waterways, or soil.
• For detailed safety information, refer to the applicable Safety Data Sheet (SDS) prior to handling.
