molecules of the month


mechanism-based SAE E1 ligase inhibitor

first-in-class, Ph. II (IV) for adv. solid tumors

from phenotypic screen and scaffold hop

J. Med. Chem., Feb. 25, 2021

Millenium/Takeda, Cambridge, MA

Chemical structure of molecule TAK-981 Subasumstat
1 min read

5. The Millenium/Takeda SUMO-activating enzyme (SAE) inhibitor TAK-981 is a mechanism-based inhibitor that covalently forms a SUMO substrate-inhibitor adduct that potently inhibits SAE, rather than reacting with SAE directly. The Takeda team has been able to successfully leverage this fascinating mechanism to develop potent inhibitors against a range of E1 enzymes including ATG7 and NEDD8-activating enzyme (NAE), one of which (pevonedistat) is currently in a Ph. III trial for AML. TAK-981 is currently in combination Ph. II trials for advanced solid tumors as an intravenous infusion. This Takeda platform is another great example of how chasing down mechanisms from a phenotypic screen can lead to a rich pipeline of new targets and clinical candidates beyond what was originally intended.

request a trial

You don’t have time to read everything, but you can’t afford to fall behind.

Drug Hunter Premium is drug discovery, distilled, so you can quickly catch up and make informed decisions based on industry examples.

Get ahead now by requesting a trial.

already a member? log in: