TAK-243 (MLN7243)

TAK-243 (MLN7243) is a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE) with an IC50 of 1 ± 0.2 nM in the UBCH10 E2 thioester assay. It has minimal inhibitory activity in a panel of kinase and receptor assays, as well as on human carbonic anhydrase type I and type II. TAK-243 (MLN7243) induces ER stress, abrogates NFκB pathway activation and promotes apoptosis.

TAK-243 (MLN7243) Chemical Structure

TAK-243 (MLN7243) Chemical Structure

CAS: 1450833-55-2

Selleck's TAK-243 (MLN7243) has been cited by 39 publications

Purity & Quality Control

Batch: Purity: 99.61%
99.61

TAK-243 (MLN7243) Related Products

Choose Selective E1 Activating Inhibitors

Biological Activity

Description TAK-243 (MLN7243) is a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE) with an IC50 of 1 ± 0.2 nM in the UBCH10 E2 thioester assay. It has minimal inhibitory activity in a panel of kinase and receptor assays, as well as on human carbonic anhydrase type I and type II. TAK-243 (MLN7243) induces ER stress, abrogates NFκB pathway activation and promotes apoptosis.
Targets
NF-κB [2] UAE [1]
(Cell-free assay)
1 nM
In vitro
In vitro

TAK-243 treatment causes depletion of cellular ubiquitin conjugates, resulting in disruption of signaling events, induction of proteotoxic stress, and impairment of cell cycle progression and DNA damage repair pathways. TAK-243 has weaker inhibitory activity against other closely related E1 ubiquitin-like activating enzymes such as Fat10-activating enzyme (UBA6; 7 ± 3 nM), NEDD8-activating enzyme (NAE; 28 ± 11 nM), SUMO-activating enzyme (SAE; 850 ± 180 nM), ISG15-activating enzyme (UBA7; 5,300 ± 2,100 nM) and autophagy-activating enzyme (ATG7; >10,000 nM) than it does against UAE. TAK-243 inhibits UAE from transferring ubiquitin to an E2 enzyme. TAK-243 shows equally potent inhibition of the two E1 enzymes capable of activating ubiquitin (UBA6 and UAE), as indicated by comparable decreases in levels of charged USE1 and UBCH10. Downstream UAE pathway inhibition by TAK-243 is evident, as shown by a dose- and time-dependent loss of both polyubiquitin chains and mono-ubiquitylated histone H2B; however, TAK-243 treatment does not affect UAE (UBE1) protein levels. TAK-243 treatment also causes accumulation of short-lived proteins such as c-Jun, c-Myc, MCL1 and p53[1].

Cell Research Cell lines HCT-116 and WSU-DLCL2 cells
Concentrations 0.01, 0.10 or 1.00 μM
Incubation Time 1, 2, 4, 8, 16 and 24 h
Method

HCT-116 and WSU-DLCL2 cells are maintained in log-phase growth in McCoy's 5A modified or RPMI-1460 medium, respectively supplemented with 10% fetal bovine serum at 37℃ in a 5% CO2 incubator. Cells are grown in 6-well cell culture dishes and treated with DMSO (0.1%) or with 0.01, 0.10 or 1.00 μM TAK-243 for the times indicated. Whole-cell extracts are prepared using RIPA buffer.

Experimental Result Images Methods Biomarkers Images PMID
Western blot poly-ubiquitin / ubiquitin / cleaved PARP PERK / GRP78 / p-eIF2α / CHOP / p-IκBα / PARP c-Myc / Mcl-1 30617217
In Vivo
In vivo

TAK-243 treatment causes death of cancer cells and, in primary human xenograft studies. TAK-243 demonstrates broad antitumor activity in models of solid and hematological tumors[1].

Animal Research Animal Models SCID mice bearing WSU-DLCL2 NHL xenograft tumors
Dosages 12.5, 18.75 and 25 mg/kg
Administration IV
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03816319 Not yet recruiting
Myelodysplastic Syndrome|Recurrent Acute Myeloid Leukemia|Refractory Acute Myeloid Leukemia|Refractory Chronic Myelomonocytic Leukemia|Refractory High Risk Myelodysplastic Syndrome
National Cancer Institute (NCI)
April 30 2024 Phase 1
NCT02045095 Terminated
Advanced Malignant Solid Tumors
Millennium Pharmaceuticals Inc.|Takeda
January 31 2014 Phase 1

Chemical Information & Solubility

Molecular Weight 519.52 Formula

C19H20F3N5O5S2

CAS No. 1450833-55-2 SDF --
Smiles N[S;v6](=O)(=O)OCC1CC(NC2=CC=NC3=CC(=N[N]23)C4=CC(=CC=C4)SC(F)(F)F)C(O)C1O
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 100 mg/mL ( (192.48 mM); Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 25 mg/mL

Water : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy TAK-243 (MLN7243) | TAK-243 (MLN7243) supplier | purchase TAK-243 (MLN7243) | TAK-243 (MLN7243) cost | TAK-243 (MLN7243) manufacturer | order TAK-243 (MLN7243) | TAK-243 (MLN7243) distributor