MT-DADMe-ImmA (MTDIA) is an inhibitor of human 5'-methylthioadenosine phosphorylase (MTAP, Ki: 90 pM).

MTAP:90 pM (Ki, cell free)

Treatment of cultured cells with MTA and MT-DADMe-ImmA inhibit MTAP, increase cellular MTA concentrations, decrease polyamines, and induce apoptosis in FaDu and Cal27, two head and neck squamous cell carcinoma cell lines. MT-DADMe-ImmA alone does not induce apoptosis in any cell line [2].

MTAP activity slowly returns, giving a biological half-life for the action of oral MT-DADMe-ImmA of 6.3 days. The time-dependent growth of FaDu tumors in immunodeficient mice is suppressed by oral or intraperitoneal treatment with MT-DADMe-ImmA [2].

Cell viability is evaluated using the Alamar Blue assay. Cells are seeded onto 96-well plates at a density of 10^4 cells/well and incubated with increasing concentrations of MT-DADMe-ImmA (100 pM to 100 μM) for 4 days at fixed MTA concentrations (0, 5, 10, and 20 μM) [2].

Tumors were established in mice for 5 days prior to oral or intraperitoneal treatments with MT-DADMe-ImmA. Mice are treated with an oral dose of 21 mg/kg or an intraperitoneal dose of 5 mg/kg/day MT-DADMe-ImmA [2].