HIT211504993 significantly inhibited tumor growth by 77% in an HCT-8 colon cancer xenograft model at 50 mg/kg, comparable to the 81% inhibition seen with SAHA.
Does HIT211504993 inhibit tumor growth in colon cancer models?
HIT211504993 is a novel, potent, and selective HDAC6 inhibitor that demonstrates significant antitumor activity in colon cancer models.
Absolute Event Rate: 77% vs 81%
Histone deacetylase (HDAC) inhibitors exert anticancer effects through epigenetic regulation. Developing HDAC inhibitors with different chemical types represents a promising anticancer treatment strategy. Herein, we established an enhanced comprehensive computational pipeline to identify tertiary benzenesulfonanilide-based HDAC inhibitor lead compounds and elucidate activity differences among derivatives based on electronic properties. Highly active HIT211504993 is a potent inhibitor selective for HDAC6 (IC50 = 0.07 μM) over HDAC2 and HDAC4. HIT211504993 (20 μM) suppresses colon cancer cell proliferation and induces apoptosis in vitro and significantly inhibits tumor growth (50 mg/kg, 77%) in an HCT-8 xenograft model, comparable to SAHA (50 mg/kg, 81%). Mechanistically, HIT211504993 inhibits Myc-driven tumorigenesis by promoting nucleocytoplasmic acetylation and modulating p53, cell-cycle, and Wnt/β-catenin signaling. The investigation of antitumor activity and its mechanism of action provides a theoretical basis for the development of the next-generation benzenesulfonanilide HDAC inhibitors.
Gao et al. (2026) studied Colon cancer. HIT211504993 vs. SAHA (50 mg/kg) was evaluated on Tumor growth inhibition in HCT-8 xenograft model. HIT211504993 significantly inhibited tumor growth by 77% in an HCT-8 colon cancer xenograft model at 50 mg/kg, comparable to the 81% inhibition seen with SAHA.