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.
TAS4464是一种高效且选择性的NEDD8激活酶（NAE）抑制剂，IC50为0.955nM。TAS4464具有优异的抗肿瘤活性，且靶点抑制作用持久[1]。TAS4464常用于急性髓系白血病[2]和多发性骨髓瘤[3]的研究。
TAS4464（0.1μM；0，8和24小时）可显著诱导急性髓系白血病HL-60细胞凋亡[2]。TAS4464（0.3-1000nM，72小时）可抑制多发性骨髓瘤细胞系的生长，并诱导其发生凋亡或有丝分裂性死亡[4]。
TAS4464（50或100mg/kg，每周两次；3周；静脉注射）显著抑制了人类多发性骨髓瘤异种移植小鼠模型中的肿瘤生长[4]。