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 under investigation in clinical trial NCT03648372 (A Study to Evaluate the Safety, Tolerability, Preliminary Efficacy and Pharmacokinetics (PK) of TAK-981 in Adult Participants With Advanced or Metastatic Solid Tumors or Relapsed/refractory Hematologic Malignancies and in a Subset With Coronavirus Disease 2019 (COVID-19)).
Subasumstat is a small molecule inhibitor of sumoylation, with potential immune-activating and antineoplastic activities. Upon intravenous administration, subasumstat targets and covalently binds to the small ubiquitin-like modifier (SUMO; small ubiquitin-related modifier) protein, forming an adduct with SUMO protein (subasumstat-SUMO adduct). This prevents the transfer of SUMO from the SUMO-activating enzyme (SAE) to SUMO-conjugating enzyme UBC9. This prevents SUMO conjugation to lysine residues on target proteins and abrogates many sumoylated protein-mediated cellular processes that play key roles in tumor cells, including proliferation, DNA repair, metastasis and survival. In addition, by preventing sumoylation, subasumstat is able to increase the production of type 1 interferon (IFN), thereby increasing type 1 IFN-mediated signaling, activating innate effector cells and enhancing the antitumor innate immune responses. This may further increase tumor cell killing. Sumoylation, a post-translational modification that attaches the SUMO protein to target proteins, plays a key role in regulating their activity, function, subcellular localization and stability. Sumoylation also plays a key role in inhibiting innate immune responses, specifically by inhibiting the pattern recognition receptor (PRR) pathway and preventing type 1 IFN expression. Abnormal sumoylation of target proteins is associated with many cancers.

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Mechanism of Action
Subasumstat binds and forms an adduct with SUMO, stopping the protein from transferring from the SUMO-activating enzyme to SUMO-conjugating enzyme UBC9. Downstream, this stops many sumoylated protein-mediated pathways from occurring in tumor cells, like DNA repair, metastasis, and proliferation. Subasumstat is also able to increase the production of type 1 interferon, which activates antitumor immune responses in cells and signals for increased 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。