MS417

MS417 is a selective BET-specific BRD4 inhibitor, binds to BRD4-BD1 and BRD4-BD2 with IC₅₀s of 30, 46 nM and K_ds of 36.1, 25.4 nM, respectively, with weak selectivity at CBP BRD (IC₅₀, 32.7 μM). IC50 & Target: IC50: 30 nM (BRD4-BD1), 46 nM (BRD4-BD2), 32.7 μM (CBP BRD)^[1]
Kd: 36.1 nM (BRD4-BD1), 25.4 nM (BRD4-BD2)^[1] In Vitro: MS417 is a BET-specific BRD4 inhibitor, binds to BRD4-BD1 and BRD4-BD2 with IC₅₀s of 30, 46 nM and K_ds of 36.1, 25.4 nM, respectively, with less selectivity at CBP BrD (IC₅₀, 32.7 μM). MS417 effectively blocks BRD4 binding to NF-κB, almost completely suppresses TNFα-induced NF-κB transcription activation in human embryonic kidney 293T cells at 1 μM and also reduces NF-κB p65 acetylation in the HIV-infected RTECs. MS417 (1 μM) modulation of gene transcription in HIV-infected human primary renal tubular epithelial cells. In addition, MS417 suppresses NF-κB-targeted cytokines and chemokines^[1]. In Vivo: MS417 (0.08 mg/kg) markedly improves renal function, reduces proteinuria and decreases glomerulosclerosis, tubular injury, and infiltration of inflammatory cells in the kidney of Tg26 mice^[1].