Subasumstat (Synonyms: TAK-981) |
Katalog-Nr.GC64972
One-Click Copy Product Info
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Subasumstat (TAK-981) ist ein erstklassiger und selektiver Inhibitor der enzymatischen SUMOylierungskaskade mit potenziell immunaktivierenden und antineoplastischen AktivitÄten.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1858276-04-6
Sample solution is provided at 25 µL, 10mM.
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Subasumstat is a selective inhibitor of the SUMOylation enzyme cascade with potent anti-leukemic activity[1]. SUMOylation is a reversible post-translational modification that is involved in the regulation of multiple cellular processes, including inflammatory responses and type 1 interferon (IFN1) expression[2]. Subasumstat can induce the expression of natural killer cell (NK cell) ligands on acute myeloid leukemia cells and activate NK cell cytotoxicity[3].
In vitro, treatment of human NK cells with Subasumstat (1μM) for 24h significantly increased the intracellular mRNA expression of interferon-γ-induced protein 10 (IP-10) and cluster of differentiation 69 (CD69)[4]. Subasumstat (1μM) treatment of T cells from patients with chronic lymphocytic leukemia (CLL) significantly reduced regulatory T cell (Treg) differentiation and induced IFNγ secretion by CD4+ and CD8+ T cells[5].
In vivo, Subasumstat (15mg/kg) was treated intravenously in THP-1 xenograft mice, which significantly inhibited tumor progression in mice, prolonged the survival of mice, and exerted a synergistic effect with 5-azacytidine (AZA)[6]. Subasumstat (25mg/kg) was treated intravenously in multiple myeloma (MM) cell xenograft mice for 7 days, which significantly inhibited tumor growth and induced apoptosis of primary MM cells[7].
References:
[1] Kotani H, Oshima H, Boucher J C, et al. Dual inhibition of SUMOylation and MEK conquers MYC-expressing KRAS-mutant cancers by accumulating DNA damage[J]. Journal of Biomedical Science, 2024, 31(1): 68.
[2] Du L, Liu W, Rosen S T, et al. Mechanism of SUMOylation-mediated regulation of type I IFN expression[J]. Journal of Molecular Biology, 2023, 435(5): 167968.
[3] Hallal R, De Toledo M, Tempe D, et al. The SUMOylation inhibitor TAK-981 (Subasumstat) triggers IFN-I-dependent activation of Natural Killer cells against Acute Myeloid Leukemias[J]. bioRxiv, 2024: 2024.02. 19.580882.
[4] Nakamura A, Grossman S, Song K, et al. The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation[J]. Blood, The Journal of the American Society of Hematology, 2022, 139(18): 2770-2781.
[5] Lam V, Roleder C, Liu T, et al. T cell–intrinsic immunomodulatory effects of TAK-981 (subasumstat), a SUMO-activating enzyme inhibitor, in chronic lymphocytic leukemia[J]. Molecular cancer therapeutics, 2023, 22(9): 1040-1051.
[6] Gabellier L, De Toledo M, Chakraborty M, et al. SUMOylation inhibitor TAK-981 (subasumstat) synergizes with 5-azacytidine in preclinical models of acute myeloid leukemia[J]. Haematologica, 2023, 109(1): 98.
[7] Heynen G J J E, Baumgartner F, Heider M, et al. SUMOylation inhibition overcomes proteasome inhibitor resistance in multiple myeloma[J]. Blood Advances, 2023, 7(4): 469-481.
| Cell experiment [1]: | |
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Cell lines |
Human NK cells |
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Preparation Method |
Human NK cells were treated with 20μg/mL AIFNAR2- and/or 1μM Subasumstat for 24h, and the mRNA expression of IP-10 and CD69 was analyzed by Western blot. |
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Reaction Conditions |
1μM; 24h |
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Applications |
Subasumstat treatment of NK cells resulted in a robust increase in IP-10 and CD69 expression without a significant impact on cell viability. |
| Animal experiment [2]: | |
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Animal models |
NSG mice |
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Preparation Method |
NSG mice were injected with THP-1 cells and treated with Subasumstat (15mg/kg, i.v.), 5-azacytidine (AZA) (2mg/kg, i.p.) or the combination. Quantification, as relative luminescence units, of tumor burden evolution monitored by luminescence intensity in mice injected with bioluminescent THP-1 cells. Overall survival after treatment start of mice injected with bioluminescent THP-1 cells was estimated in each group and compared using Kaplan-Meier method and log-rank test. |
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Dosage form |
15mg/kg; i.v. |
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Applications |
Subasumstat and AZA monotherapy limited tumor progression in THP-1 and significantly prolonged the survival of mice. The combination of Subasumstat+AZA had a higher anti-leukemic effect than monotherapy. |
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References: |
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| Cas No. | 1858276-04-6 | SDF | |
| Überlieferungen | TAK-981 | ||
| Formula | C25H28ClN5O5S2 | M.Wt | 578.1 |
| Löslichkeit | DMSO : 16.67 mg/mL (28.84 mM; ultrasonic and warming and heat to 80°C) | 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 | 1.7298 mL | 8.649 mL | 17.298 mL |
| 5 mM | 346 μL | 1.7298 mL | 3.4596 mL |
| 10 mM | 173 μL | 864.9 μL | 1.7298 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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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 saline, 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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)