TAK-243

Inhibitor of UBA1

Structure

Information

Protein target names: UBA1

Mechanism of action: Inhibitor

Recommended in-cell concentration:
0.01, 0.10 or 1.00 μM
Primary References:

In Vitro Validations

Uniprot ID: P22314
Target Class: Other post-translational modification
Target SubClass: Ubiquitin-conjugating enzyme
Potency: Kd
Potency Value: >0.75 nM
Potency Assay: E1–UBL-dependent pyrophosphate exchange (PPiX) activity
PDB ID for probe-target interaction (3D structure): 5TR4 5L6J
Structure-activity relationship: yes
Target aliases:
Ubiquitin-like modifier-activating enzyme 1, UBE1, ...

DOI Reference: 10.1038/nm.4474

Uniprot ID: P22314
Target Class: Other post-translational modification
Target SubClass: Ubiquitin-conjugating enzyme
Potency: IC50
Potency Value: 1 ± 0.2 nM
Potency Assay: UBCH10 E2 transthiolation assay
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Ubiquitin-like modifier-activating enzyme 1, UBE1, ...

DOI Reference: 10.1038/nm.4474

In Cell Validations

In Vivo Data

I have extra information to add

SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

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

In Cell Rating
In Model Organisms

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 )