TAK-243
Inhibitor of UBA1
Structure
In Cells
In Model Organisms
Probe TAK-243 is in the process of SERP review.
Please continue to check back for new reviews and commentary.
Information
Protein target names: UBA1
Mechanism of action: Inhibitor
In Vitro Validations
DOI Reference: 10.1038/nm.4474
DOI Reference: 10.1038/nm.4474
In Cell Validations
In Vivo Data
SERP ratings and comments
SERP Ratings
Comments:
TAK-243 is a potent inhibitor of UAE which demonstrates complete inhibition of cellular ubiquitylation and sub-micromolar anti-proliferative activity against multiple cancer cell lines. Robust antitumor activity has been achieved in murine subcutaneous xenograft studies via IV or SC administration.
(last updated: 20 May 2021 )
SERP Ratings
Comments:
TAK-243 is a potent inhibitor of UBA1 with cellular activities consistent with the proposed mechanism of action. TAK-243 shows anti-tumor activity in mouse xenograft studies at doses at or below the maximum tolerated dose. Although TAK-243 is a potent inhibitor of the UBA1-related enzymes UBA6 and UBA3 (NEDD8-activating enzyme), these off-target activities are reported not to contribute to the anti-tumor efficacy of TAK-243. Users should consider whether activity against UBA6 or UBA3 will impact their own studies.
TAK-243 may be suitable for interrogating Uba1 in yeast as well as in mammalian cells: structural studies show that the yeast enzyme is inhibited by the same mechanism as the mammalian enzyme. Potency and selectivity in yeast is not yet established.
(last updated: 18 Jun 2021 )