Subasumstat (TAK-981) 刺激 1 型干扰素的合成，进而刺激 1 型干扰素介导信号的产生，激活先天效应细胞，并增强免疫系统对肿瘤的防御能力 [1]。

DC 激活是通过将 Subasumstat (TAK-981) 单次皮下注射到 Balb/c 电极臂中来诱导的 [2]。

[1]. Sumoylation inhibitor TAK-981.

[2]. TAK-981.

Subasumstat is being investigated in the clinical trial NCT03648372 (a study evaluating the safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of TAK-981 in adult patients with advanced or metastatic solid tumors or relapsed/refractory hematologic malignancies, as well as in a COVID-19 subgroup). Subasumstat is a small molecule SUMOylation inhibitor with potential immune-activating and antitumor activity. After intravenous administration, Subasumstat targets and covalently binds to small ubiquitin-like modified proteins (SUMO), forming an adduct with SUMO proteins (Subasumstat-SUMO adduct). This prevents SUMO from transferring from SUMO-activating enzyme (SAE) to SUMO-conjugating enzyme UBC9. This prevents SUMO from binding to lysine residues on the target protein and inhibits many SUMOylation-mediated cellular processes that play crucial roles in tumor cells, including proliferation, DNA repair, metastasis, and survival. Furthermore, by inhibiting SUMOylation, sulfinamide can increase the production of type I interferon (IFN), thereby enhancing IFN-mediated signaling, activating innate immune effector cells, and strengthening the anti-tumor innate immune response. This may further enhance the killing power of tumor cells. SUMOylation is a post-translational modification that links SUMO proteins to target proteins, playing a crucial role in regulating the activity, function, subcellular localization, and stability of target proteins. SUMOylation also plays a key role in suppressing the innate immune response, particularly by inhibiting the pattern recognition receptor (PRR) pathway and blocking the expression of type I IFN. Aberrant SUMOylation of target proteins is associated with various cancers.

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Mechanism of Action
Subasumstat binds to SUMO and forms an adduct, preventing the translocation of proteins from SUMO-activating enzymes to the SUMO-conjugating enzyme UBC9 downstream. This inhibits many SUMOylated protein-mediated signaling pathways in tumor cells, such as DNA repair, metastasis, and proliferation. Subasumstat can also increase the production of type I interferon, thereby activating the intracellular anti-tumor immune response and signaling to promote tumor cell death.

C25H28CLN5O5S2

578.1033

577.122

1858276-04-6

(S)-Subasumstat;1858282-76-4

118628567

White to light yellow solid powder

1.474±0.06 g/cm3(Predicted)

836.1±75.0 °C(Predicted)

3.5

193

4

11

8

38

942

4

CC1=C(C=C(S1)C(=O)C2=CN=CN=C2N[C@@H]3C[C@@H]([C@H](C3)O)COS(=O)(=O)N)[C@H]4C5=C(CCN4)C=CC(=C5)Cl

LXRZVMYMQHNYJB-UNXOBOICSA-N

InChI=1S/C25H28ClN5O5S2/c1-13-18(23-19-7-16(26)3-2-14(19)4-5-29-23)9-22(37-13)24(33)20-10-28-12-30-25(20)31-17-6-15(21(32)8-17)11-36-38(27,34)35/h2-3,7,9-10,12,15,17,21,23,29,32H,4-6,8,11H2,1H3,(H2,27,34,35)(H,28,30,31)/t15-,17-,21+,23+/m1/s1

[(1R,2S,4R)-4-[(5-[4-[(1R)-7-Chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl)amino]-2-hydroxycyclopentyl]methyl sulfamate

TAK-981; TAK 981; TAK981

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~16.67 mg/mL (~28.84 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.32 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 2.5 mg/mL (4.32 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (4.32 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。