TAS4464 is a highly potent and selective inhibitor of NEDD8-activating enzyme (NAE), with an IC50 of 0.955nM. TAS4464 exhibits superior antitumor activity with prolonged target inhibition[1]. TAS4464 is commonly used in the study of acute myeloid leukemia[2] and multiple myeloma[3].
TAS4464 (0.1μM; 0, 8, and 24h) significantly induced apoptosis in acute myeloid leukemia HL-60 cells[2]. TAS4464 (0.3-1000nM, 72h) inhibits cell growth and induces apoptotic or mitotic cell death in multiple myeloma cell lines[4].
TAS4464 (50 or 100mg/kg, twice a week; 3 weeks; i.v.) significantly inhibited tumor growth in human multiple myeloma xenograft mouse model[4].
References:
[1] Yoshimura C, Muraoka H, Ochiiwa H, et al. TAS4464, a highly potent and selective inhibitor of NEDD8-activating enzyme, suppresses neddylation and shows antitumor activity in diverse cancer models[J]. Molecular Cancer Therapeutics, 2019, 18(7): 1205-1216.
[2] Ochiiwa H, Ailiken G, Yokoyama M, et al. TAS4464, a NEDD8-activating enzyme inhibitor, activates both intrinsic and extrinsic apoptotic pathways via c-Myc-mediated regulation in acute myeloid leukemia[J]. Oncogene, 2021, 40(7): 1217-1230.
[3] Muraoka H, Yoshimura C, Tsuji S, et al. TAS4464, a novel highly potent NEDD8 activating enzyme inhibitor, demonstrates antitumor activity in multiple myeloma through the inactivation of NF-κB pathways[J]. Cancer Research, 2015, 75(15_Supplement): 1730-1730.
[4] Muraoka H, Yoshimura C, Kawabata R, et al. Activity of TAS4464, a novel NEDD8 activating enzyme E1 inhibitor, against multiple myeloma via inactivation of nuclear factor κB pathways[J]. Cancer Science, 2019, 110(12): 3802-3810.