Discovery and evaluation of novel Benzohydroxamic acid-indole derivatives as dual inhibitors of ADAM17 and HDAC2 with antitumor activity.

Hepatocellular carcinoma (HCC) has garnered significant attention from researchers due to its high recurrence rate and invasive characteristics. The design of drugs with dual-target combined effects represents a promising strategy in cancer treatment. Our observations suggest that ADAM17 and HDAC may inhibit the unfavorable prognostic signaling pathway Notch1 in HCC through distinct mechanisms, thereby suppressing tumor cell proliferation and metastasis.

Effect and mechanism of novel HDAC inhibitor ZDLT-1 in colorectal cancer by regulating apoptosis and inflammation.

Background: Histone deacetylase (HDAC) is a potential target for Colorectal Cancer (CRC) molecular target therapy, dehydroharmine derivative ZDLT-1 was designed to inhibit CRC cell proliferation by inhibiting HDAC target. This study aimed to explore the effect of ZDLT-1 could induce apoptosis in CRC in vitro and in vivo, and determine the mechanism of ZDLT-1.

Methods: First, MTT assay, colony formation, wound healing, Transwell assay, Hoechst33342 staining and Annexin V-FITC/PI double staining assay were used to investigate the in vitro effect of ZDLT-1.

The ADAM17 inhibitor ZLDI-8 sensitized hepatocellular carcinoma cells to sorafenib through Notch1-integrin β-talk.

ZLDI-8 is an A disintegrin and metalloproteinase domain 17 (ADAM17) inhibitor that suppresses the shedding of Notch1 to the Notch1 intracellular domain (NICD). In previous studies, we found that ZLDI-8 was able to sensitize HCC to sorafenib, but the mechanism of action remains unclear. The sensitizing effects of ZLDI-8 were tested both in vitro and in vivo.