General
Preferred name
TAK-243
Synonyms
AOB87172 ()
MLN7243 ()
AOB 87172 ()
MLN-7243 ()
TAK-243 (MLN7243) ()
Uae inhibitor mln7243 ()
Mln7243 ()
Tak 243 ()
P&D ID
PD103145
CAS
1450833-55-2
Tags
available
probe
drug candidate
Drug indication
Neoplasm
Solid tumour/cancer
Drug Status
investigational
Max Phase
1.0
Probe info
Probe type
experimental probe
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
1
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
COMMENT
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. May 20 2021 - 1:06pm; 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. Jun 18 2021 - 10:05am
DESCRIPTION
TAK-243 (MLN7243) is a first-in-class, selective ubiquitin activating enzyme, UAE (UBA1) inhibitor (IC50=1 nM), which blocks ubiquitin conjugation, disrupting monoubiquitin signaling as well as global protein ubiquitination. TAK-243 (MLN7243) induces endoplasmic reticulum (ER) stress, abrogates NF-¦ÊB pathway activation and promotes apoptosis[1][2].
PRICE
156
MOA
Inhibitor
(Chemical Probes.org)
DESCRIPTION
TAK-243 (MLN7243) is a selective inhibitor of the ubiquitin-activating enzyme UAE (IC50=1 nM), blocking ubiquitin binding and disrupting both mono-ubiquitin signaling and overall protein ubiquitination. TAK-243 exhibits antitumor activity and promotes apoptosis.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
14
Cayman Chemical Bioactives
ChEMBL Drugs
Chemical Probes.org
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugMAP
High-quality chemical probes
Mcule NIBR MoA Box Subset
MedChem Express Bioactive Compound Library
Novartis Chemogenetic Library (NIBR MoA Box)
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
17
Molecular Weight
519.09
Hydrogen Bond Acceptors
10
Hydrogen Bond Donors
4
Rotatable Bonds
7
Ring Count
4
Aromatic Ring Count
3
cLogP
1.75
TPSA
152.07
Fraction CSP3
0.37
Chiral centers
4.0
Largest ring
6.0
QED
0.34
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
NF-¦ÊB
Apoptosis
E1/E2/E3 Enzyme
NF-κB
UBA1
Apoptosis related,E1 Activating,NF-¦ÊB
Member status
member
MOA
Ubiquitin-Activating Enzyme E1 Inhibitors
ubiquitin activating enzyme inhibitor
Orthogonal probe
ABPA3
Pathway
Metabolic Enzyme/Protease
Ubiquitination
Target class
Other post-translational modification
Target subclass
Ubiquitin-conjugating enzyme
Source data
