CIB-L43 is a TRBP inhibitor. CIB-L43 exhibits a nanomolar inhibitory activity with an EC₅₀ of 0.66 nM and a dissociation constant (K_D) of 4.78 nM, indicating strong binding affinity to TRBP. CIB-L43 effectively disrupts the TRBP-Dicer interaction, with an IC₅₀ of 2.34 μM, leading to suppression of oncogenic miR-21 biosynthesis. This suppression results in increased expression of PTEN and Smad7, thereby inhibiting AKT and TGF-β signaling pathways, which are essential for hepatocellular carcinoma (HCC) cell proliferation and migration. In vivo studies demonstrate that CIB-L43 has favorable pharmacokinetics, including 53.9% oral bioavailability, and exhibits antitumor efficacy comparable to sorafenib, a first-line anticancer drug, but with lower toxicity. These findings position CIB-L43 as a promising candidate for HCC treatment, combining potent TRBP inhibition with favorable drug-like properties.
