Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions

Table 2 Reported covalent NAE inhibitors

Number	IC₅₀ (enzymatic level)	Target	IC₅₀ (cellular level)	Cell line	Year	References
1 (MLN4924)	4.00 nM	NAE	52.48–5552.47 nM	MV-4-11, LNCaP, COLO 205, THP-1, HGC27, SW620, etc.	2009	[42]
2	2.80 μM	Pan-E1	Unknown	HCT-116	2011	[118]
3	< 10.00 nM	NAE	160.00 nM	K562	2011	[119]
4	< 10.00 μM	Pan-E1	Unknown	A549, LNCap, MCF7, HeLa	2013	[120]
5	1.06 μM	NAE	12.30 − 29.50 μM	Caco-2, MCF-7, Bcl-7402	2014	[121]
6	< 0.10 μM	NAE, UAE	2.50 μM	A549	2015	[122]
7 (TAS4464)	0.96 nM	NAE	1.60–460.00 nM	Patient-derived AML cells	2019	[114]
8	0.55 nM	NAE	33.90–482.00 nM	HCT-116, HuTu80, Capan-1, MV-4–11, THP-1, etc.	2021	[123]
9	0.36 nM	NAE	5.59–2164.76 nM	SW48, COLO 205, Capan-1, THP-1, MV-4-11, HCT-116, etc.	2022	[124]

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