Subasumstat (TAK-981) stimulates the synthesis of type 1 interferons, which in turn stimulates the generation of type 1 interferon-mediated signals, activates innate effector cells, and strengthens the immune system's defense against tumors [1].

DC activation is induced by a single subcutaneous injection of Subasumstat (TAK-981) into the arm of a Balb/c electrode [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.

---

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

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: 2.5 mg/mL (4.32 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)