Examples include ubiquitin activation by E1 enzymes that can be blocked by the small molecule PYR41, which has demonstrated antileukemic activity in mouse models [186]; E1 enzyme NEDD8-activating enzyme (NAE) can be inhibited to blunt the activation of the NF-κB pathway, DNA damage, and cell death in lymphoma and AML xenograft models [187,188]. The gene discussed is NFKB1; the disease is acute myeloid leukemia.