ARV-771 CAS 1949837-12-0 98 Percent Purity PROTAC BET Degrader for Epigenetics and Cancer Research

1. Product Overview

ARV-771 (CAS No. 1949837-12-0) is a potent, orally bioavailable PROTAC (Proteolysis Targeting Chimera) designed to induce the degradation of BET (Bromodomain and Extra-Terminal) proteins, including BRD2, BRD3, and BRD4. It links a pan-BET bromodomain ligand to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase recruiter via a tailored linker. ARV-771 exhibits Kd values of 34 nM, 4.7 nM, 8.3 nM, 7.6 nM, 9.6 nM, and 7.6 nM for BRD2(1), BRD2(2), BRD3(1), BRD3(2), BRD4(1), and BRD4(2), respectively. By promoting ubiquitin-mediated proteasomal degradation rather than mere competitive inhibition, it potently suppresses MYC expression and downstream oncogenic transcription in castration-resistant prostate cancer, AML, and other malignancies driven by BET-dependent gene programs. As a clinical-stage PROTAC reference compound, it is widely used for epigenetic reader domain studies and degrader optimization.

2. Key Features and Advantages

• Pan-BET Degradation Potency: DC50 values in low nanomolar range for BRD2, BRD3, and BRD4 across multiple cell lines; effectively depletes BET proteins within hours of treatment.

• Structure-Based PROTAC Design: Combines a high-affinity BET ligand (based on JQ1 scaffold) with VHL ligand and optimized polyethylene-glycol-derived linker for efficient ternary complex formation.

• Superior to Bromodomain Inhibitors: Outperforms classical BET inhibitors (e.g., JQ1) in suppressing MYC transcription and inducing apoptosis in CRPC and hematologic malignancy models.

• Oral Bioavailability: Demonstrated oral PK in preclinical species, supporting in vivo efficacy studies at 30 to 100 mg/kg dosing.

• Research-Grade Quality: ≥98% purity (HPLC), white to light yellow solid, suitable for biochemical, cellular, and in vivo epigenetic research.

3. Main Applications

• Epigenetics & Chromatin Biology: Studying BET protein function as readers of acetylated histones; probing transcriptional regulation of oncogenes such as MYC, BCL2, and CDK4/6.

• Cancer Research: Castration-resistant prostate cancer (CRPC), acute myeloid leukemia (AML), multiple myeloma, and triple-negative breast cancer models dependent on BET signaling.

• PROTAC Technology Development: Serving as the canonical BET degrader reference for linker optimization, ternary complex characterization, and comparison with newer degraders (e.g., ARV-825, MZ1).

• Drug Combination Studies: Evaluating synergy with AR degraders (e.g., ARV-766), SOS1 inhibitors, PI3K/AKT inhibitors, or immunotherapy in solid tumors and hematologic malignancies.

• Resistance Mechanism Dissection: Comparing BET degradation versus bromodomain occupancy inhibition to understand adaptive resistance in targeted cancer therapy.

4. Technical Specifications

5. Storage and Handling

• Powder Storage: Store at -20°C in a tightly sealed container with desiccant, protected from light. Stable for up to 2–3 years under these conditions; short-term at 4°C acceptable for several months.

• Solution Storage: Prepare stock in anhydrous DMSO at 10–25 mg/mL (sonication + mild warming to 37–60 °C if needed). Aliquot to avoid freeze-thaw cycles; store at -80°C for up to 6 months or -20°C for up to 1 month.

• Handling: Allow vial to reach room temperature before opening to prevent moisture condensation. Weigh in a fume hood wearing nitrile gloves. For in vivo dosing, formulate in 10% DMSO with 90% saline or corn oil; sonicate to clarity at 1–5 mg/mL.

• Shipping: Stable for ambient-temperature shipping with desiccant and blue ice recommended for long-distance transport.

6. Safety Overview

• Intended Use: For laboratory research use only. Not for human or veterinary therapeutic, diagnostic, food, or cosmetic use.

• Hazard Profile: GHS07 warning symbol; H302 (harmful if swallowed), H315/H319 (skin/eye irritation), H335 (respiratory irritation). Handle as bioactive PROTAC with potential cytotoxicity.

• Precautions: Wear nitrile gloves, safety goggles, and lab coat. Avoid inhalation of dust, skin/eye contact, and ingestion. Use in well-ventilated area or fume hood when weighing.

• Disposal: Dispose as hazardous organic chemical waste per local regulations; do not discharge into drains or environment.

• Note: Include vehicle (DMSO/saline or corn oil) controls in all cell-based and animal experiments; monitor for off-target effects at high concentrations.