BMS-502 CAS 2407854-18-4 White to Off White Solid 98 Percent Purity DGKa and DGKzeta Dual

1. Product Overview

BMS-502 (CAS No. 2407854-18-4), systematically named 8-(4-(Bis(4-fluorophenyl)methyl)piperazin-1-yl)-5-methyl-7-nitro-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile, is a potent, selective dual inhibitor of diacylglycerol kinases alpha (DGKα) and zeta (DGKζ), with IC50 values of 4.6 nM and 2.1 nM respectively. As a small-molecule immunomodulator (MW 516.50, C27H22F2N6O3), it blocks DGK-mediated conversion of diacylglycerol (DAG) to phosphatidic acid, thereby relieving DAG-dependent TCR signaling suppression and enhancing T-cell receptor (TCR) signaling, cytokine production, and antitumor T-cell immunity in vivo. Originally disclosed by Bristol Myers Squibb via phenotypic optimization, BMS-502 serves as a key pharmacological tool for tumor immunotherapy research, CAR-T enhancement studies, and dissecting lipid-second-messenger regulation in lymphocytes.

2. Key Features and Advantages

• Ultra-Potent DGK Dual Blockade: IC50 = 4.6 nM (DGKα), 2.1 nM (DGKζ); >100-fold selectivity over a broad kinase panel including DGKβ/γ/δ/ε/η/θ/ι and other lipid kinases.

• Enhances T-Cell Immunity: Restores DAG accumulation at immunological synapses, amplifies TCR signaling, increases IL-2/IFN-γ production, and boosts CD8+ T-cell killing of tumor cells in murine models.

• Synergizes with Immunotherapy: Demonstrated combination benefit with PD-1/PD-L1 checkpoint inhibitors and CAR-T constructs to overcome T-cell exhaustion in solid tumors.

• Favorable Drug-Like Profile: MW 516.50, cLogP moderate, orally bioavailable in preclinical species; suitable for both in vitro T-cell assays and in vivo syngeneic tumor models.

• Research-Grade Quality: ≥98% purity (HPLC), white to off-white solid, stable powder at -20°C for years.

3. Main Applications

• Tumor Immunotherapy Research: Studying DGKα/ζ as checkpoint targets in melanoma, colorectal cancer, and other solid tumors; evaluating DGK inhibition to reverse T-cell anergy.

• CAR-T and TCR Engineering: Using BMS-502 to enhance CAR-T cell persistence, cytokine release, and antitumor potency in vitro and in PDX models.

• Lipid Signaling in Lymphocytes: Dissecting DAG–PKC–Ras axis vs PA–mTOR pathways controlled by DGK; monitoring pERK, pS6, NFAT nuclear translocation upon DGK blockade.

• Combination Immune Studies: Synergy screens with anti-PD-1, anti-CTLA-4, IL-15 agonists, or SOS1/KRAS inhibitors in immuno-oncology pipelines.

• Drug Discovery Reference: Serving as the lead DGK dual inhibitor for PROTAC design (DGK degraders), structure-activity optimization, and comparator in immunometabolism programs.

4. Technical Specifications

5. Storage and Handling

Store powder at -20°C in a tightly sealed, desiccated container protected from light; stable for 2–3 years. Prepare DMSO stock at 10–25 mg/mL (sonicate + warm to 37 °C if needed); aliquot to avoid freeze-thaw and store at -80°C up to 6 months or -20°C up to 1 month. For in vivo, formulate in 10% DMSO with 90% saline or 5% DMSO/PEG400/Tween80 vehicle; sonicate to clarity at 1–5 mg/mL. Allow vial to reach room temperature before opening; weigh in fume hood with nitrile gloves and goggles.

6. Safety Overview

For laboratory research use only, not for human/veterinary therapeutic or diagnostic use. GHS07 possible (H302 harmful if swallowed, H315/H319 skin/eye irritant). Handle as bioactive immunomodulatory small molecule; wear nitrile gloves, goggles, lab coat; avoid dust inhalation and contact. Dispose as organic chemical waste per local regulations. Include DMSO/saline vehicle controls in all T-cell and animal assays.