Subasumstat (Synonyms: TAK-981) |
カタログ番号GC64972
One-Click Copy Product Info
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SubasumstatはSUMOylation酵素カスカートの選択性阻害剤であり、有力な抗白血病活性を持つ。
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はSUMOylation酵素カスカートの選択性阻害剤であり、有力な抗白血病活性を持つ[1]。SUMOylationは可逆的な翻訳後修飾であり、炎症反応とタイプ1インターフェロン(IFN1)発見を含む、複数の細胞プロセスの調節に関与している[2]。Subasumstatは急性骨髄白血病で、ナチュラルキラー細胞（NK細胞）の発見を誘発でき、NK細胞の細胞毒性を活性化できる[3]。
体外では、Subasumstat (1μM)でヒトNK細胞を24時間処理した結果、インターフェロン-γ-誘発のタンパク質10(IP-10)と分化69（CD69）のクラスターの細胞内mRNA発見を著しく増やした[4]。慢性リンパ性白血病(CLL)の患者由来のT細胞をSubasumstat (1μM)で処理した結果、調節T細胞(Treg)の分化を著しく減らし、CD4+とCD8+ T細胞でIFNγ分泌を誘発した[5]。
生体内では、Subasumstat (15mg/kg)をTHP-1異種移植マウスに静脈内注射した結果、マウスで腫瘍進行を著しく阻害し、マウスの生存を伸ばし、5-azacytidine (AZA)と共に相乗効果を発揮した[6]。Subasumstat (25mg/kg)は多発性骨髄腫(MM)細胞異種移植マウスに7日間静脈内処理した結果、著しく腫瘍の成長を阻害し、初代MM細胞のアポトーシスを誘発した[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.
| 細胞実験[1]: | |
細胞株 | ヒトNK細胞 |
準備方法 | ヒトNK細胞を、20μg/mLのAIFNAR2-と/または1μMのSubasumstatで24時間処理し、IP-10とCD69のmRNA発見をウエスタンブロットで分析した。 |
反応条件 | 1μM；24時間 |
アプリケーション | NK細胞をSubasumstatで処理した結果、細胞の生存率に衝撃を与えずに、IP-10とCD69の発見を急激に増やした。 |
| 動物実験 [2]: | |
動物モデル | NSGマウス |
準備方法 | NSGマウスにTHP-1細胞を注射し、Subasumstat (15mg/kg、静脈内)、5-azacytidine (AZA) (2mg/kg、腹腔内)、またはその併用で処理した。生物発光THP-1細胞を注入したマウスの発光強度で監視された腫瘍負荷の進行を、相対発光単位として定量化する。生物発光THP-1細胞を注入されたマウスの、処理開始後の総生存率を、各グループで測定し、Kaplan-Meier法とログランク検定で比較した。 |
投与形態 | 15mg/kg；静脈内投与 |
アプリケーション | SubasumstatとAZAの単独療法は、THP-1で腫瘍の進行を制限し、マウスの生存を著しく伸ばした。単独療法に比べて、Subasumstat+AZAの併用は、より高い抗白血病効果を持った。 |
References: | |
| Cas No. | 1858276-04-6 | SDF | |
| 同義語 | TAK-981 | ||
| Formula | C25H28ClN5O5S2 | M.Wt | 578.1 |
| 溶解度 | 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 | |||
|
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 |
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Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- 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.)