1. Product Overview
Indirubin-3′-monoxime (CAS 83141-96-2), systematically named (E)-N-hydroxy-2-(1H-indol-3-ylmethylene)-1H-indol-3-imine 3′-oxime, is a water-soluble derivative of indirubin—the active component of the traditional Chinese medicine formula Danggui Longhui Wan used for chronic myelogenous leukemia. With the molecular formula C₁₆H₁₂N₃O₂ and a molecular weight of 278.29 g/mol, it appears as an orange-red to brick red crystalline powder. Indirubin-3′-monoxime inhibits cyclin-dependent kinase 2 (CDK2)/Cyclin E with IC₅₀ ≈ 180 nM and glycogen synthase kinase-3β (GSK-3β) with IC₅₀ ≈ 5–10 nM, while showing markedly reduced activity against CDK4/Cyclin D1 and CDK1/Cyclin B. It arrests cells at G1/S and G2/M checkpoints, induces apoptosis, and promotes β-catenin degradation via GSK-3β activation—making it valuable for studying cell cycle control, Wnt/β-catenin signaling, and neurodegenerative tauopathy models. 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
• Dual CDK2/GSK-3β inhibition: Potent CDK2/Cyclin E inhibition (IC₅₀ ~180 nM) and GSK-3β inhibition (IC₅₀ 5–10 nM); >50-fold selectivity over CDK4/Cyclin D1 and CDK1/Cyclin B at 5 µM.
• Improved solubility vs indirubin: The 3′-oxime group confers ~100× better aqueous solubility (~50–100 µM directly in culture medium vs <1 µM for parent indirubin), enabling straightforward cell culture dosing without co-solvent precipitation.
• Cell cycle & Wnt pathway probe: Induces G1/S and G2/M arrest, reduces Cyclin E levels, activates GSK-3β (dephosphorylates Ser9), promotes β-catenin degradation—useful for dissecting Wnt/β-catenin vs CDK dependencies.
• Pro-apoptotic & anti-proliferative: Triggers caspase-3/7 activation, PARP cleavage, and mitochondrial depolarization in K562, MCF-7, HeLa; less toxic to non-transformed fibroblasts at equivalent doses.
• High purity: Typically ≥98% by HPLC (suppliers offer 98–99%+), suitable for MTT/CCK-8, flow cytometry (PI/Annexin V), Western blot (p27^Kip1, Cyclin E, p-GSK-3β Ser9, β-catenin, cleaved caspase-3), and kinase assays.
• Consistent batch quality with supporting analytical data (HPLC, LC-MS, NMR) available; referenced in J. Biol. Chem. 2001 (Hoessel et al. – indirubins), Biochemistry 2006 (Meijer et al.), and Alzheimer's GSK-3β literature.
3. Main Applications
• Cell cycle & CDK research: Evaluating CDK2/Cyclin E inhibition on S-phase entry, p27^Kip1 induction, and G1/S checkpoint control in cancer and normal cells.
• GSK-3β / neurodegeneration studies: Testing GSK-3β inhibition effects on tau phosphorylation (reduced p-tau Ser396/404), amyloid-β production, and neuronal survival in primary cortical/hippocampal neurons and AD mouse models.
• Wnt/β-catenin signaling: Assessing β-catenin stabilization/destabilization via GSK-3β activity modulation; comparing with LiCl or CHIR99021 in reporter (TOP/FOP-Flash) assays.
• Antitumor mechanism: Assessing indirubin analog–induced apoptosis, autophagy, and multidrug-resistance modulation in leukemia (K562, Jurkat), breast (MCF-7), and liver (HepG2) cancer lines.
• Traditional medicine & natural product SAR: Comparing parent indirubin, indirubin-3′-monoxime, and indirubin-3′-oxime derivatives for structure–activity relationships in kinase inhibition.
4. Technical Specifications
5. Storage and Handling
• Store the powdered compound sealed with desiccant, protected from light (amber vial or foil-wrapped); recommended storage at -20°C (long term 2 years) or 4°C (≤6 months). For DMSO stock solutions, aliquot and store at -20°C or -80°C wrapped in foil (6 months stable); avoid repeated freeze–thaw cycles. Typical working stocks are 5 mM or 10 mM in anhydrous DMSO; for cell treatment, dilute directly into medium (final DMSO ≤0.1%).
• Before opening, allow the sealed vial to warm to room temperature to prevent moisture condensation. Keep container tightly closed and wrapped in aluminum foil 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. Solutions stain plastics/glass orange-red.
• Intended exclusively for laboratory research by qualified personnel; not for human or veterinary use, food, drug, or cosmetic applications (despite historical TCM relevance—this is research-grade only).
6. Safety Overview
• Indirubin-3′-monoxime is a bioactive kinase inhibitor with cytotoxicity in the low micromolar range (IC₅₀ 0.5–5 µM in many cancer lines). Treat as potentially hazardous: may cause irritation to eyes, skin, and respiratory system; possible skin sensitizer.
• 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; work under reduced light due to photosensitivity.
• Dispose of in accordance with local regulations for hazardous chemical and natural product derivative waste. Do not discharge into drains, waterways, or soil.
• For detailed safety information, refer to the applicable Safety Data Sheet (SDS) prior to handling.
