CD28-IN-3

CD28-IN-3 is a CD28 inhibitor with an IC50 of 7.80 μM and a Kd of 52.45 μM. It selectively disrupts the CD28-B7 interaction, thereby inhibiting CD28-mediated costimulatory signaling. CD28-IN-3 enhances the production of pro-inflammatory cytokines IFN-γ, IL-2, and TNF-α. This compound is utilized in research on checkpoint-resistant cancers.

CD28-IN-3 (Compound 22VS) inhibits the interaction between membrane-bound CD28-CD80 and CD28-CD86 in CHO-K1 cells at concentrations ranging from 0-100 μM for 2 hours, achieving submicromolar IC 50 values of 1.48 μM and 1.39 μM, respectively. At concentrations of 10-300 μM, CD28-IN-3 exhibits no cytotoxicity to human Jurkat T lymphocytes after 24 hours of incubation. Additionally, CD28-IN-3 suppresses CD28-mediated T cell costimulation in a Jurkat-Raji co-culture system with an IC 50 of 6.96 μM when applied at 0-200 μM for 5 hours. In a dose-dependent manner (10-50 μM; 48 h), CD28-IN-3 inhibits the release of CD28-dependent pro-inflammatory cytokines (IFN-γ, IL-2, TNF-α) in a 3D A549 tumor-PBMC co-culture system and a human PBMC-mucosal co-culture system.