TAK-243 (MLN7243) (Synonyms: TAK-243) |
| Catalog No.GC32737 |
TAK-243 (MLN7243) is a selective inhibitor of ubiquitin activating enzyme (UBA1) with an IC50 value of 1nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1450833-55-2
Sample solution is provided at 25 µL, 10mM.
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TAK-243 (MLN7243) is a selective inhibitor of ubiquitin activating enzyme (UBA1) with an IC50 value of 1nM[1]. TAK-243 can block ubiquitin binding, disrupt monoubiquitin signaling and global protein ubiquitination, and is currently used as an anticancer drug in clinical trials[2]. TAK-243 can induce endoplasmic reticulum stress (ERS) response, eliminate NF-κB pathway activation, and promote cell apoptosis[3].
In vitro, TAK-243 (0-1000nM) treatment of SLFN11 wild-type (WT) and SLFN11 knockout (KO) prostate cancer DU145, hepatocellular carcinoma Li-7 and leukemia MOLT4 cells for 72h inhibited cell viability in a concentration-dependent manner. SLFN11-KO cells were significantly more sensitive to TAK-243 than their WT counterparts[4]. TAK-243 (0-100nM) was used to treat multiple myeloma cell lines (MM1.S and MOLP-8 TP53 wild-type cells) for 24h, with an IC50 value of approximately 25nM, which significantly increased the levels of intracellular cleaved caspase-3, -8, and -9 and reduced the content of ubiquitin-protein conjugates[5].
In vivo, TAK-243 (10, 20mg/kg) was used to treat H295R cell xenograft mice by intraperitoneal injection for 29 days, which significantly inhibited tumor growth, reduced the expression level of ubiquitinated proteins in tumor tissues, and induced tumor cell apoptosis[6]. TAK-243 (20mg/kg) was used to treat acute myeloid leukemia (AML) cell xenograft mice by subcutaneous injection for 3 weeks, which reduced the AML tumor burden and the levels of monoubiquitinated and polyubiquitinated proteins in tumor tissues[7].
References:
[1] Hyer M L, Milhollen M A, Ciavarri J, et al. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment[J]. Nature medicine, 2018, 24(2): 186-193.
[2] Best S, Hashiguchi T, Kittai A, et al. Targeting ubiquitin-activating enzyme induces ER stress–mediated apoptosis in B-cell lymphoma cells[J]. Blood advances, 2019, 3(1): 51-62.
[3] Wang G, Fan F, Sun C, et al. Looking into endoplasmic reticulum stress: the key to drug-resistance of multiple myeloma?[J]. Cancers, 2022, 14(21): 5340.
[4] Murai Y, Jo U, Murai J, et al. SLFN11 inactivation induces proteotoxic stress and sensitizes cancer cells to ubiquitin activating enzyme inhibitor TAK-243[J]. Cancer research, 2021, 81(11): 3067-3078.
[5] Zhuang J, Lee H, Kuiatse I, et al. The anti-tumor effect of the ubiquitin-activating enzyme (UAE) inhibitor TAK-243 on pre-clinical models of multiple myeloma[J]. 2016.
[6] Arakawa Y, Jo U, Kumar S, et al. Activity of the ubiquitin-activating enzyme inhibitor TAK-243 in adrenocortical carcinoma cell lines, patient-derived organoids, and murine xenografts[J]. Cancer Research Communications, 2024, 4(3): 834-848.
[7] Barghout S H, Patel P, Wang X, et al. TAK-243 is a selective UBA1 inhibitor that displays preclinical activity in acute myeloid leukemia (AML)[J]. Blood, 2017, 130: 814.
| Cell experiment [1]: | |
Cell lines | DU145、Li-7、MOLT4 cells (SLFN11 wild-type (WT) and SLFN11 knockout (KO)) |
Preparation Method | Cells were plated in 96-well white plates. After 24-hours incubation, TAK-243 (0-1000nM) was added and incubated for 72h. Cell viability was measured using EnVision™ with ATPlite solution. |
Reaction Conditions | 0-1000nM; 72h |
Applications | TAK-243 inhibited cell viability in a concentration-dependent manner, and SLFN11-KO cells were significantly more sensitive to TAK-243 than their WT counterparts. |
| Animal experiment [2]: | |
Animal models | NSG mice |
Preparation Method | A total of 4×106 H295R cells were suspended in 100μL of Matrigel and inoculated subcutaneously into the right flank of NSG female mice. One week later, mice were divided into three groups (vehicle, TAK-243 10mg/kg, TAK-243 20mg/kg intraperitoneally twice weekly; n=5 per group). Xenograft diameters and mouse weights were measured weekly, and on day 29 all mice were euthanized, and xenografts were harvested. |
Dosage form | 10, 20mg/kg; 29 days; i.p. |
Applications | TAK-243 treatment significantly inhibits tumor growth, reduces ubiquitinated proteins, and induces apoptosis in H295R xenografts. |
References: | |
| Cas No. | 1450833-55-2 | SDF | |
| Synonyms | TAK-243 | ||
| Canonical SMILES | O=S(OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](NC2=CC=NC3=CC(C4=CC=CC(SC(F)(F)F)=C4)=NN23)C1)(N)=O | ||
| Formula | C19H20F3N5O5S2 | M.Wt | 519.52 |
| Solubility | DMSO : 50 mg/mL (96.24 mM);Water : 1 mg/mL (1.92 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9249 mL | 9.6243 mL | 19.2485 mL |
| 5 mM | 0.385 mL | 1.9249 mL | 3.8497 mL |
| 10 mM | 0.1925 mL | 0.9624 mL | 1.9249 mL |
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