[2] "Inhibition of NAE prevents activation of cullin-RING ligases (CRLs), which are critical for proteasome-mediated protein degradation.

"[3] MLN4924 has been shown to disrupt CRL-mediated protein turnover leading to apoptosis in cancer cells by deregulating S-phase DNA synthesis.

In a phase 1 trial to determine dosing in patients with AML and myelodysplastic syndromes "modest clinical activity was observed".

[6] Later, in 2016, pevonedistat demonstrated a significant therapeutic effect in three further Phase I clinical cancer trials.

These include pevonedistat trials against relapsed/refractory multiple myeloma or lymphoma,[7] metastatic melanoma,[8] and advanced solid tumors.