TAK-243 (MLN7243)

Catalog No.S8341 Batch:S834103

Technical Data

Formula

C₁₉H₂₀F₃N₅O₅S₂

Molecular Weight

519.52

CAS No.

1450833-55-2

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (192.48 mM)

Ethanol

6 mg/mL (11.54 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

5.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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

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].

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].

Protocol (from reference)

Cell Assay:^{^[1]}	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.
Animal Study:^{^[1]}	Animal Models SCID mice bearing WSU-DLCL2 NHL xenograft tumors Dosages 12.5, 18.75 and 25 mg/kg Administration IV

Cell Assay:^{^[1]}

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.

Animal Study:^{^[1]}

Animal Models
SCID mice bearing WSU-DLCL2 NHL xenograft tumors
Dosages
12.5, 18.75 and 25 mg/kg
Administration
IV

References

Selleck's TAK-243 (MLN7243) has been cited by 43 publications

A structure-based designed small molecule depletes hRpn13Pru and a select group of KEN box proteins [ Nat Commun, 2024, 15(1):2485]	PubMed: 38509117
hnRNPA2B1 represses the disassembly of arsenite-induced stress granules and is essential for male fertility [ Cell Rep, 2024, 43(2):113769]	PubMed: 38363675
SUMOylation modulates eIF5A activities in both yeast and pancreatic ductal adenocarcinoma cells [ Cell Mol Biol Lett, 2024, 29(1):15]	PubMed: 38229033
The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation [ Science, 2023, 381(6660):eadh5021]	PubMed: 37616343
ESCRT-dependent STING degradation inhibits steady-state andcGAMP-induced signalling [ Nature Communications, 2023, Article-number:-611-2023)]	PubMed: None
An adaptive stress response that confers cellular resilience to decreased ubiquitination [ Nat Commun, 2023, 10.1038/s41467-023-43262-7]	PubMed: 37963875
ESCRT-dependent STING degradation inhibits steady-state and cGAMP-induced signalling [ Nat Commun, 2023, 14(1):611]	PubMed: 36739287
K6-linked ubiquitylation marks formaldehyde-induced RNA-protein crosslinks for resolution [ Mol Cell, 2023, 10.1016/j.molcel.2023.10.011]	PubMed: 37951215
Termination of STING responses is mediated via ESCRT-dependent degradation [ EMBO J, 2023, 42(12):e112712]	PubMed: 37139896
Actionable loss of SLF2 drives B-cell lymphomagenesis and impairs the DNA damage response [ EMBO Mol Med, 2023, e16431.]	PubMed: 37485814

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SHIPPING AND STORAGE
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