BRD4/NAMPT-IN-1 (Compound A2) shows strong inhibitory effects on NAMPT and BRD4 (IC50=35 nM (NAMPT) and 58 nM (BRD4)). BRD4/NAMPT-IN-1 inhibits the growth and migration of hepatocellular carcinoma cells and promotes apoptosis. BRD4/NAMPT-IN-1 also shows potent anticancer effects in HCCLM3 xenograft mouse model, with no obvious toxic effects.
BRD4/NAMPT-IN-1 exhibits IC50 values of 12 nM for BRD4(BD1) and 41 nM for BRD4(BD2) against other members of the BET family[1].BRD4/NAMPT-IN-1 inhibits the proliferation of cancer cells with IC50 of 2.37 μM (Hep3B), 6.49 μM (Huh7), 5.44 μM (HCCLM3) and 9.51 μM (LX-2), respectively[1].BRD4/NAMPT-IN-1 (1-10 μM; 72 h) on Hep3B cells shows that: 1: it can inhibit the expression of oncogenes up-regulated by BRD4, and at the same time reduces the levels of NAPRT and NAMPT. 2: It significantly increases cell arrest at G0/G1 phase. 3: It dose-dependently induces apoptosis. 4: It dose-dependently inhibits the migratory ability of the cells[1].BRD4/NAMPT-IN-1 (1-10 μM; 72 h) dose-dependently reduces NAD + concentration in Hep3B cells and HCCLM3 cells[1].
BRD4/NAMPT-IN-1 (i.p.; 40 mg/kg/day and 80 mg/kg/day; 27 days) exhibits dose-dependent tumor suppression in HCCLM3 xenograft nude mice[1].
References:
[1]. Yin C, et al. Discovery of potent and novel dual NAMPT/BRD4 inhibitors for efficient treatment of hepatocellular carcinoma. Eur J Med Chem. 2024 May 5;271:116444.