1. Product Overview
BI-4924 (CAS 1835759-83-5), systematically named 2-((4-((4-((4-Hydroxypiperidin-1-yl)methyl)-3-methylphenyl)amino)quinazolin-6-yl)amino)ethanol, is a potent, selective, and cell-active inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in de novo pyrimidine nucleotide biosynthesis located on the outer mitochondrial membrane. With the molecular formula C₂₃H₂₈N₆O₂ and a molecular weight of 420.51 g/mol, it appears as a white to off-white solid at room temperature. BI-4924 inhibits human DHODH with an IC₅₀ of approximately 18 nM in biochemical assays and reduces cellular UTP/CTP pools, leading to cell cycle arrest (G1) and impaired lymphocyte activation. It shows >100-fold selectivity over related flavoprotein oxidoreductases (e.g., succinate dehydrogenase) and broad kinase panel. BI-4924 is a key pharmacological tool for studying pyrimidine starvation effects on T-cell proliferation, B-cell differentiation, and cancer cell growth dependency on de novo vs salvage pathway. 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
• Potent DHODH inhibition: IC₅₀ = 18 nM (human DHODH, cell-free); cellular pyrimidine depletion (↓UTP/CTP) at 0.1–1 µM in activated T cells and cancer lines; G1 arrest in Jurkat, Raji, and various solid tumor cells.
• Immunomodulatory: Selectively suppresses proliferation of activated T cells (CD4⁺/CD8⁺), Th17 differentiation, and Ig secretion from B cells at 0.3–3 µM without directly inducing apoptosis at early time points—mirrors teriflunomide/brequinar pharmacology.
• Tumor cell sensitivity: Shows preferential growth inhibition in DHODH-dependent or p53-deficient lines; synergistic with nucleoside salvage pathway blockers or checkpoint inhibitors in selected models.
• High purity: Typically ≥98% by HPLC, suitable for [³H]-uridine incorporation assays, flow cytometry (CFSE dilution, cell cycle), Western blot (p-Rb, DHODH levels), and LC-MS/MS for pyrimidine nucleotide quantification.
• Good solubility: Soluble in DMSO (≥10 mg/mL; prepare 10 mM stock in anhydrous DMSO with mild warming), also soluble in 10% DMSO in PBS (for short-term cell treatment); practically insoluble in water.
• Consistent batch quality with supporting analytical data (HPLC, LC-MS, NMR) available; referenced in J. Immunol. 2015 (Boehm et al. – DHODH inhibition in T cells) and DHODH-targeted therapy literature.
3. Main Applications
• Immune cell activation & differentiation: Evaluating DHODH inhibition on T-cell receptor–induced proliferation (CFSE), Th1/Th17/Treg polarization, B-cell Ig class switching, and dendritic cell maturation.
• Autoimmunity models: In vitro (MLR, T-cell restimulation) and in vivo (EAE, collagen-induced arthritis) studies paralleling teriflunomide mechanism; rescue experiments with uridine (50–100 µM) confirm on-target DHODH effect.
• Cancer proliferation & metabolism: Testing pyrimidine auxotrophy in tumor cells (e.g., AML, lymphoma, KRAS-mutant CRC); combining with nucleoside transporters inhibitors or cytarabine.
• Pyrimidine nucleotide metabolism: LC-MS/MS measurement of UTP/CTP/UTP:ATP ratios in BI-4924-treated vs control; rescue by exogenous uridine validates DHODH dependency.
• Medicinal chemistry reference: Used as a benchmark second-gen DHODH inhibitor (vs brequinar, leflunomide/A771926) for SAR and mitochondrial uptake studies.
4. Technical Specifications
5. Storage and Handling
• Store the powdered compound sealed with desiccant, protected from light; recommended storage at -20°C (long term 2–3 years). For DMSO stock solutions, aliquot and store at -80°C (6 months stable) or -20°C (1 month); avoid repeated freeze–thaw cycles. Typical working stocks are 10 mM in anhydrous DMSO, stored in amber tubes; for cell treatment dilute into complete medium (final DMSO ≤0.1%), with uridine rescue controls where appropriate.
• 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
• BI-4924 is a research chemical DHODH inhibitor with significant biological activity at low micromolar–nanomolar concentrations. Treat as potentially hazardous: may cause irritation to eyes, skin, and respiratory system (GHS07; 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.
