1. Product Overview
PT-179 (CAS 2924858-25-1), systematically named 2-(2,6-dioxopiperidin-3-yl)-5-morpholinoisoindoline-1,3-dione, is a novel thalidomide-derived molecular glue degrader that selectively binds to the E3 ubiquitin ligase Cereblon (CRBN). With the molecular formula C₁₇H₁₇N₃O₅ and a molecular weight of 343.33 g/mol, it appears as a light yellow to yellow powder at room temperature. Unlike traditional immunomodulatory drugs (IMiDs) such as lenalidomide or pomalidomide, PT-179 does not induce the degradation of endogenous Ikaros (IKZF1) or Aiolos (IKZF3), thereby eliminating major off-target effects associated with clinical CRBN modulators. PT-179 forms a productive ternary complex with CRBN and a genetically encoded "compact degradation tag" (comprising a zinc finger domain), enabling precise, conditional, and reversible degradation of user-defined target proteins. It is a cutting-edge tool for developing orthogonal protein degradation platforms in mammalian cells. 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
• Novel Orthogonal Molecular Glue: Selectively engages CRBN without degrading endogenous neosubstrates (IKZF1/3), overcoming a key limitation of IMiD-based PROTACs/degraders.
• Compact Degradation Tag System: Functions with a minimal zinc finger (ZF) fusion tag (~6 kDa), significantly smaller than traditional tags (e.g., HaloTag, dTAG), minimizing interference with target protein folding and function.
• High Specificity & Reversibility: Induces rapid and reversible degradation of tagged proteins upon dosing; washout leads to quick recovery of protein levels, ideal for studying essential genes and dynamic processes.
• High Purity: Typically ≥98% by HPLC, suitable for cell-based assays, Western blot validation, and live-cell imaging studies.
• Good Solubility: Readily soluble in DMSO (preparing 10–50 mM stock solutions is standard), facilitating robust cellular screening and dose-response experiments.
• Well-Characterized: Validated in literature (e.g., Nat. Chem. Biol. 2023) for constructing "degradation-on-demand" systems in diverse cell types, including primary cells and iPSCs.
3. Main Applications
• Synthetic Biology & Chemical Genetics: Development of compact, inducible protein degradation systems for functional genomics screens and precise control of protein abundance.
• Target Validation: Rapid assessment of phenotype rescue and target engagement in disease models by toggling protein levels on/off without genetic manipulation.
• Drug Discovery Tool: Serves as a parent scaffold for designing next-generation molecular glues with tailored specificity or as a positive control in CRBN recruitment assays.
• Cellular Dynamics Research: Studying the kinetics of protein turnover, localization, and interactions in real-time using reversible degradation switches.
• General Research: Used as a reference standard in medicinal chemistry programs focusing on E3 ligase modulation and targeted protein degradation (TPD).
4. Technical Specifications
5. Storage and Handling
• Store the powdered compound sealed with desiccant, protected from light; recommended storage at -20°C (long term). For DMSO stock solutions, aliquot and store at -80°C to maintain stability; avoid repeated freeze–thaw cycles. Typical working stocks are 10 mM or 50 mM in anhydrous DMSO.
• 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
• PT-179 is a research chemical with limited toxicological data. 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.
