653592-04-2

Ki: 90 pM (MTAP)

Treatment of cultured cells with MT-DADMe-ImmA and MTA inhibit MTAP, increase cellular MTA concentrations, decrease polyamines, and induce apoptosis in FaDu and Cal27, two head and neck squamous cell carcinoma cell lines. The same treatment does not induce apoptosis in normal human fibroblast cell lines (CRL2522 and GM02037) or in MCF7, a breast cancer cell line with an MTAP gene deletion. MT-DADMe-ImmA alone does not induce apoptosis in any cell line, implicating MTA as the active agent.

The t _1/2 for onset of inhibition is 50 min with complete inhibition by 250 min. 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.