TMLB-C16

TMLB-C16 is a potent and orally active B3GAT3 inhibitor with a K D of 3.962 μM. TMLB-C16 suppresses proliferation and migration, and induces cell cycle arrest and apoptosis in MHCC-97H ( IC₅₀ = 6.53 μM) and HCCLM3 cells ( IC₅₀ = 6.22 μM). TMLB-C16 inhibits tumor growth in both MHCC-97H and HCCLM3 xenograft tumor mouse models without causing obvious toxicity. TMLB-C16 can be used for hepatocellular carcinoma research ^[1].

In Vivo, TMLB-C16 (5, 10 and 20 mg/kg, i.g., daily from day 7 to day 31) inhibits tumor growth in both MHCC-97H and HCCLM3 xenograft tumor mouse models^[1].

In Vitro, TMLB-C16 (72 h) demonstrates broad antitumor activities in 13 B3GAT3 high expressed cancer cell lines (such as NCI-H460, NCI-H1650, and Calu3 cells) in a B3GAT3-dependent manner, with IC₅₀ values below 20 μM^[1]. TMLB-C16 (0-10 μM, 14 days) prevents colony formation in a dose-dependent manner in MHCC-97H and HCCLM3 cells^[1]. TMLB-C16 (0-10 μM, 24 h) inhibits cell migration and inhibits cell division in MHCC-97H and HCCLM3 cells^[1]. TMLB-C16 (0-10 μM, 48 h) induces G0/G1-phase cell cycle arrest and apoptosis in MHCC-97H and HCCLM3 cells in a dose-dependent manner, accompanied by enhanced p21, p53, and retinoblastoma-associated protein (Rb) levels and decreased CDK6, cyclin E1, and phosphorylated-Rb (p-Rb) levels^[1].

References:
[1]. Yin H, et al. Discovery of Novel 2-Oxoacetamide Derivatives as B3GAT3 Inhibitors for the Treatment of Hepatocellular Carcinoma. J Med Chem. 2024 Jul 11;67(13):10743-10773.