AMXT-1501 tetrahydrochloride

AMXT-1501 tetrahydrochloride is an orally active polyamine transport inhibitor. AMXT1501 blocks tumor growth in immunocompetent mice but not in athymic nude mice lacking T cells^[1]. Combination of DFMO and AMXT-1501 induces caspase-3 mediated apoptosis in NB cell lines^[2]. IC50 & Target:Polyamine transport^[1] In Vitro: AMXT-1501 tetrahydrochloride (0.39-50 μM; 48 hours) treatment exhibits cytotoxicity against this panel of NB cell lines (BE(2)-C, SMS-KCNR and SH-SY5Y cells), with IC₅₀ values of 17.72 μM for SMS-KCNR, 17.69?μM for BE(2)-C, and 14.13?μM for SH-SY5Y^[2].
BE(2)-C, SMS-KCNR and SH-SY5Y cells are exposed to AMXT-1501 tetrahydrochloride (2.5 μM) and DFMO (2.5 mM) alone or in combination (AMXT-1501 tetrahydrochloride 2.5 μM + DFMO 2.5 mM). After 96 hours exposure to AMXT-1501 tetrahydrochloride or DFMO does not significantly alter the level of noncleaved PARP, cleaved PARP and cleaved caspase 3, whereas cells treated with the combination of AMXT-1501 tetrahydrochloride with DFMO decrease the amount of noncleaved PARP and increase the amount of cleaved PARP and cleaved caspase 3^[2]. In Vivo: AMXT-1501 tetrahydrochloride (3 mg/kg; subcutaneous injection; every day; 28 days) alone is sufficient to delay EAE onset moderately,but fails to protect animals from reaching the endpoint. However, the combination of DFMO and AMXT-1501 tetrahydrochloride are sufficient to deplete T cell polyamine pool, and consequently suppress T cell proliferation and effector function in vivo^[3].