TAK-243

SKU: orb1307707

Description

TAK-243 (MLN7243) is a potent and selective inhibitor of the ubiquitin-activating enzyme (UAE/UBA1) with an IC50 of 1 nM. It effectively blocks global protein ubiquitination, disrupting key cellular signaling pathways. This mechanism underlies its observed pro-apoptotic and antitumor effects in both in vitro and in vivo cancer research models.

Research Area

Cell Biology, Epigenetics & Chromatin, Protein Biochemistry, Signal Transduction

Key Properties

• CAS Number: 1450833-55-2
• MW: 519.52
• Purity: 98.93% (May vary between batches)
• Formula: C₁₉H₂₀F₃N₅O₅S₂
• SMILES: NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ccnc3cc(nn23)-c2cccc(SC(F)(F)F)c2)[C@H](O)[C@@H]1O
• Target: Apoptosis,E1/E2/E3 Enzyme,NF-κB
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (9.62 mM);DMSO:237.5 mg/mL (457.15 mM)

Bioactivity

• Target IC50:
  myeloma cell:25-100 nM|panel of cells derived from hematologic and solid tumors:0.006 μM to 1.31 μM (EC50)|OCI-AML2 cells、TEX cells、U937 cells、 NB4 cells:15-40 nM|UBA1:1 nM|MM.1S cells:25 nM
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• In Vivo:
  METHODS: To assay antitumor activity in vivo, TAK-243 (12.5 mg/kg twice weekly; or 25 mg/kg once weekly) was administered intravenously for two weeks to SCID mice bearing myeloma MM1.S or MOLP-8. S and MOLP-8 models, twice-weekly administration of 12.5 mg/kg produced 60% and 73% tumor growth inhibition at 14 days. 25 mg/kg produced a greater effect. METHODS: To test the antitumor activity in vivo, TAK-243 (20 mg/kg) was injected intravenously twice weekly into SCID mice bearing the human AML tumor OCI-AML2. RESULTS: TAK-243 significantly delayed tumor growth (T/C=0.02) in mice without toxicity.
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• In Vitro:
  METHODS: Seven myeloma cells were treated with TAK-243 (6.25-500 nM) for 24 h. Cell viability was measured by WST-1 Assay. RESULTS: Most myeloma cells are very sensitive to TAK-243 with IC50 of 25-100 nM, e.g. MM1.S cells with IC50 of 25 nM. METHODS: Human colorectal cancer cells HCT-116 were treated with TAK-243 (0.008-1 µM) for 24 h, and the expression levels of target proteins were detected by Western Blot. RESULTS: TAK-243 showed strong selectivity for Sumo and autophagic UBL pathways, and TAK-243 inhibited two E1 enzymes (UBA6 and UAE), which are capable of activating ubiquitin, with equal potency.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Apoptosis, E3Enzyme, E2 conjugating enzyme, E2 Enzyme, E2Enzyme, E3 Enzyme, E3 ligating enzyme, E1 activating enzyme, E1 Enzyme, E1/E2/E3 Enzyme, E1Enzyme, Inhibitor, inhibit, NF-κB, NFκB, NF-kB, NFkB, MLN 7243, MLN7243, MLN-7243, Nuclear factor-kappaB, Nuclear factor-κB, UBA1, Ubiquitin activating enzyme, Ubiquitin conjugating enzyme, Ubiquitin ligase, TAK 243, TAK243, TAK-243

Compound Identifiers

PubChem CID

71715374