ARV-393 CAS 2851885-95-3 98 Percent Purity PROTAC BCL6 Degrader for Non Hodgkin Lymphoma and BCL6 Signaling Research

1. Product Overview

ARV-393 (CAS No. 2851885-95-3) is a potent, orally bioavailable PROTAC (Proteolysis Targeting Chimera) designed to induce degradation of B-cell lymphoma 6 (BCL6), a key oncogenic transcription factor in diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), and other non-Hodgkin lymphomas. It couples a high-affinity BCL6 BTB domain ligand to a Cereblon (CRBN) E3 ubiquitin ligase recruiter via an optimized linker. ARV-393 drives ubiquitin-mediated proteasomal degradation of BCL6 with DC50 and GI50 values below 1 nM in multiple DLBCL and BL cell lines, while sparing related BTB-domain proteins such as BACH2 and promyelocytic leukemia zinc finger (PLZF). In vivo, oral dosing at 30 to 100 mg/kg achieves robust tumor regression in DLBCL xenograft models, making it a clinical-stage PROTAC reference for lymphoma research and degrader optimization.

2. Key Features and Advantages

• Sub-nanomolar BCL6 Degradation: DC50 < 1 nM in DLBCL/BL cell lines; completely depletes BCL6 protein within 4 to 6 hours of treatment.

• High Selectivity: Does not degrade related BTB proteins (BACH2, PLZF, BAZF) or off-target transcription factors; >1000-fold selectivity over wild-type BCL6 BTB interactors.

• Oral Bioavailability: Demonstrated oral PK in mice and rats with good exposure and tolerability; suitable for chronic in vivo dosing studies.

• Proven In Vivo Efficacy: Induces durable tumor regression in DLBCL PDX and CDX models at 30 to 100 mg/kg QD oral gavage, outperforming BCL6 peptide inhibitors.

• Research-Grade Quality: ≥98% purity (HPLC), white to off-white solid, optimized for cell-based assays, flow cytometry, and animal pharmacology.

3. Main Applications

• Non-Hodgkin Lymphoma Research: DLBCL, Burkitt lymphoma, and follicular lymphoma models dependent on BCL6 transcriptional program.

• PROTAC Technology Development: Reference BCL6 degrader for ternary complex studies, linker optimization, and comparison with ARV-825 (BRD4) or ARV-771 (BET).

• Transcription Factor Degradation: Probing feasibility of degrading oncogenic transcription factors via Cereblon recruitment in hematologic malignancies.

• Drug Combination Studies: Synergy with BTK inhibitors, BCL2 antagonists (venetoclax), or immune checkpoint blockade in lymphoma models.

• Mechanistic BCL6 Dissection: Monitoring downstream target genes (e.g., MYC, CCND1, CDK6) upon BCL6 removal to distinguish degrader vs inhibitor effects.

4. Technical Specifications

5. Storage and Handling

Store powder at -20°C in a sealed, desiccated container protected from light; stable for 2 to 3 years. Prepare DMSO stock at 10 to 25 mg/mL with brief sonication and warming to 37–60 °C; aliquot to avoid freeze-thaw and store at -80°C up to 6 months or -20°C up to 1 month. For in vivo oral gavage, formulate in 10% DMSO with 90% saline or corn oil at 1 to 5 mg/mL, sonicate to clarity. Allow vial to reach room temperature before opening; weigh in fume hood with nitrile gloves.

6. Safety Overview

For laboratory research use only, not for human/veterinary therapeutic or diagnostic use. GHS07 hazard (H302 harmful if swallowed, H315/H319 skin/eye irritant, H335 respiratory irritant). Wear nitrile gloves, goggles, lab coat; avoid dust inhalation and contact. Dispose as organic chemical waste per local rules. Include vehicle controls in all assays.