TAS4464

TAS4464 is a highly potent and selective small molecule inhibitor of the NEDD8 activating enzyme (NAE), with an IC50 of approximately 0.955 nM. By inhibiting NAE, TAS4464 prevents the neddylation of cullin proteins, leading to inactivation of cullin-RING ubiquitin E3 ligases (CRLs). This results in accumulation of CRL substrates such as CDT1 and p27, disruption of cell cycle progression, induction of apoptosis, and inhibition of nuclear factor κB (NF-κB) signaling pathways including both canonical and non-canonical pathways. TAS4464 has demonstrated antitumor activity in multiple myeloma models and various human cancer cell lines. It was developed primarily for treatment against advanced solid tumors and hematologic malignancies like multiple myeloma. Clinical evaluation includes phase 1 trials investigating safety, dose-limiting toxicities, pharmacokinetics, and preliminary efficacy.

Other names

TAS-4464TAS4464TAS 4464