Target Validation Information
TTD ID	T96311
Target Name	NEDD8-activating enzyme E1C (UBA3)
Type of Target	Literature-reported
Drug Potency against Target		Drug Info	IC50 = 4 nM	[1]
Action against Disease Model		Drug Info	Inhibition of NEDD8-activating enzyme (NAE) by the small molecule NAE inhibitor MLN4924 leads to increased steady-state levels of direct Cullin-RING ligase (CRL) substrates by preventing their ubiquitination and proteasome-dependent degradation. Many of these CRL substrates are involved in cell cycle progression, including a critical DNA replication licensing factor CDT1. Cell cycle analysis of asynchronous and synchronous cultures after NAE inhibition revealed effects on cell cycle distribution and activation of DNA break repair signaling pathways similar to that reported for CDT1 overexpression.	[2]
References
REF 1	An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732-6.
REF 2	Inhibition of NEDD8-activating enzyme induces rereplication and apoptosis in human tumor cells consistent with deregulating CDT1 turnover. Cancer Res. 2011 Apr 15;71(8):3042-51.

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