1. Product Overview
KI-696 Isomer (CAS 1799974-69-8), systematically named (R)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid, is the low-affinity stereoisomer of the potent KEAP1–NRF2 protein–protein interaction inhibitor KI-696. With the molecular formula C₂₈H₃₀N₄O₆S and a molecular weight of 550.63 g/mol, it appears as a white to off-white solid at room temperature. While the parent compound KI-696 binds KEAP1 with Kd = 1.3 nM, this (3R)-configured isomer exhibits >100-fold reduced binding affinity (Kd >150 nM) and minimal ability to disrupt KEAP1–NRF2 interaction or induce NRF2 nuclear translocation at comparable concentrations. It serves as an essential negative control/isomer control to confirm on-target effects of KI-696 in cell-based and biochemical assays. 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
• Low-activity negative control: >100-fold reduced KEAP1 binding vs active KI-696; fails to induce NRF2 stabilization or ARE-reporter activation at concentrations where KI-696 is fully effective—ideal for confirming target specificity.
• Matched physicochemical properties: Same molecular weight, solubility, and formulation behavior as KI-696, ensuring comparable cellular uptake and vehicle effects when used side-by-side.
• High purity: Typically ≥98% by HPLC (suppliers offer 98–99%+), suitable as a paired control in Western blot (NRF2, NQO1, HO-1), qPCR, and cell viability studies.
• Good solubility: Soluble in DMSO (≥125 mg/mL), ethanol (≥100 mg/mL); practically insoluble in water; compatible with same stock preparation protocol as KI-696.
• Consistent batch quality with supporting analytical data (HPLC, LC-MS, chiral HPLC, NMR) available from qualified suppliers; typically supplied alongside KI-696 for SAR and mechanism-of-action validation.
• Enables clean target deconvolution: Rules out non-specific cytotoxicity or off-target kinase effects when comparing KI-696 vs isomer in dose–response experiments.
3. Main Applications
• Negative control for KI-696 studies: Paired with KI-696 to validate that observed NRF2 activation, HO-1/NQO1 upregulation,, and cytoprotection are KEAP1–NRF2 interaction–specific rather than nonspecific effects.
• Stereochemical SAR validation: Demonstrating the importance of the (S)-configuration at the propanoic acid α-carbon for KEAP1 Kelch domain recognition in fragment-based inhibitor design.
• Oxidative stress & COPD research: Used in parallel with KI-696 in tBHP-challenge or cigarette smoke extract models to confirm on-target antioxidant gene induction.
• General NRF2 pathway dissection: Helps distinguish NRF2-dependent vs NRF2-independent outcomes of putative KEAP1 inhibitors in cancer, neurodegeneration, and inflammation models.
• Medicinal chemistry reference: Benchmark inactive enantiomer for chiral optimization in KEAP1–NRF2 PPI inhibitor programs.
4. Technical Specifications
5. Storage and Handling
• Store the powdered compound sealed with desiccant, protected from light; recommended storage at -20°C (long term 3 years). For DMSO stock solutions, aliquot and store at -80°C wrapped in foil (2 years stable) or -20°C (1 year); avoid repeated freeze–thaw cycles. Typical working stocks are 10 mM or 50 mM in anhydrous DMSO, matched to KI-696 preparation.
• 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
• KI-696 Isomer is a research chemical with limited toxicological data but known low biological activity at KEAP1. Treat as potentially hazardous: may cause irritation to eyes, skin, and respiratory system (GHS07; H302/H315/H319/H335).
• 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.
