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Chemical Structure| 1450833-55-2 Chemical Structure| 1450833-55-2

Structure of TAK-243
CAS No.: 1450833-55-2

Chemical Structure| 1450833-55-2

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TAK-243, also known as MLN7243 and AOB87172, is a small molecule inhibitor of ubiquitin-activating enzyme (UAE), with potential antineoplastic activity.

Synonyms: MLN7243

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Product Citations

Product Citations

Wu, Changyong ; Shen, Yang ; Shi, Lin ; Zhang, Junhao ; Guo, Tongxuan ; Zhou, Lingni , et al.

Abstract: Glioblastoma multiforme (GBM) is a brain tumor with high mortality and recurrence rate. Radiotherapy and chemotherapy after surgery are the main treatment options available for GBM. However, patients with glioblastoma have a grave prognosis. The major reason is that most GBM patients are resistant to radiotherapy. UBA1 is considered an attractive potential anti-tumor therapeutic target and a key regulator of DNA double-strand break repair and genome replication in human cells. Therefore, we hypothesized that TAK-243, the firstin-class UBA1 inhibitor, might increase GBM sensitivity to radiation. The combined effect of TAK-243 and ionizing radiation on GBM cell proliferation, and colony formation ability was detected using CCK-8, colony formation, and EdU assays. The efficacy of TAK-243 combined with ionizing radiation for GBM was further evaluated in vivo, and the mechanism of TAK-243 sensitizing radiotherapy was preliminarily discussed. The results showed that TAK-243, in combination with ionizing radiation, significantly inhibited GBM cell proliferation, colony formation, cell cycle arrest in the G2/M phase, and increased the proportion of apoptosis. In addition, UBA1 inhibition by TAK-243 substantially increased the radiationinduced γ-H2AX expression and impaired the recruitment of the downstream effector molecule 53BP1. Therefore, TAK-243 inhibited the radiation-induced DNA double-strand break repair and thus inhibited the growth of GBM cells. Our results provided a new therapeutic strategy for improving the radiation sensitivity of GBM and laid a theoretical foundation and experimental basis for further clinical trials.

Keywords: GBM ; TAK-243 ; radiosensitization ; DNA damage repair ; cell apoptosis

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Product Details of TAK-243

CAS No. :1450833-55-2
Formula : C19H20F3N5O5S2
M.W : 519.52
SMILES Code : 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
Synonyms :
MLN7243
MDL No. :MFCD28964160
InChI Key :KJDAGXLMHXUAGV-DGWLBADLSA-N
Pubchem ID :71715374

Safety of TAK-243

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02045095 Advanced Malignant Solid Tumor... More >>s Less << PHASE1 TERMINATED 2016-11-09 Boston, Massachusetts, United ... More >>States|Saint Louis, Missouri, United States|Cleveland, Ohio, United States|Philadelphia, Pennsylvania, United States|Charleston, South Carolina, United States|Nashville, Tennessee, United States|San Antonio, Texas, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.92mL

0.38mL

0.19mL

9.62mL

1.92mL

0.96mL

19.25mL

3.85mL

1.92mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

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