Subasumstat

Subasumstat
Clinical data
Drug class	SUMOylation inhibitor
Identifiers
	IUPAC name [(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;
CAS Number	1858276-04-6;
PubChem CID	118628567;
IUPHAR/BPS	11305;
DrugBank	DB16406;
ChemSpider	72380106;
UNII	XQ43H3V6M1;
KEGG	D12268;
ChEMBL	ChEMBL4862901;
Chemical and physical data
Formula	C25H28ClN5O5S
Molar mass	546.04 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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;
	InChI 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; Key:LXRZVMYMQHNYJB-UNXOBOICSA-N;

Subasumstat (TAK-981) is a drug that acts as a SUMOylation inhibitor. By preventing cellular proteins from being stabilised by conjugation with SUMO proteins, it makes it more difficult for cancer cells to maintain genomic stability during repeated cell divisions. It has been researched for the treatment of leukemia, as well as other forms of cancer.^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]

References

↑ Nakamura A, Grossman S, Song K, Xega K, Zhang Y, Cvet D, et al. (May 2022). "The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation". Blood. 139 (18): 2770–2781. doi:10.1182/blood.2021014267. PMC 11022956. PMID 35226739.
↑ Heynen GJ, Baumgartner F, Heider M, Patra U, Holz M, Braune J, et al. (February 2023). "SUMOylation inhibition overcomes proteasome inhibitor resistance in multiple myeloma". Blood Advances. 7 (4): 469–481. doi:10.1182/bloodadvances.2022007875. PMC 9979771. PMID 35917568.
↑ Lam V, Roleder C, Liu T, Bruss N, Best S, Wang X, et al. (September 2023). "T Cell-intrinsic Immunomodulatory Effects of TAK-981 (Subasumstat), a SUMO-activating Enzyme Inhibitor, in Chronic Lymphocytic Leukemia". Molecular Cancer Therapeutics. 22 (9): 1040–1051. doi:10.1158/1535-7163.MCT-22-0762. PMC 10525033. PMID 37420267.
↑ Gabellier L, De Toledo M, Chakraborty M, Akl D, Hallal R, Aqrouq M, et al. (January 2024). "SUMOylation inhibitor TAK-981 (subasumstat) synergizes with 5-azacytidine in preclinical models of acute myeloid leukemia". Haematologica. 109 (1): 98–114. doi:10.3324/haematol.2023.282704. PMC 10772526. PMID 37608777.
↑ Assouline SE, Mehta A, Hanel W, Doucet S, Johnston PB, Danilov A, et al. (November 2025). "Phase I/II Study of Subasumstat (TAK-981) in Combination With Rituximab in Relapsed/Refractory Non-Hodgkin Lymphoma". Clinical Lymphoma, Myeloma & Leukemia. 25 (11): 788–799.e11. doi:10.1016/j.clml.2025.04.020. PMID 40467383.
↑ Juric D, Anderson D, Dowlati A, Rodon J, Lugowska I, Mańdziuk S, et al. (November 2025). "A First-In-Human Study of the SUMOylation Inhibitor Subasumstat in Patients with Advanced/Metastatic Solid Tumors or Relapsed/Refractory Hematologic Malignancies". Cancer Research Communications. 5 (11): 2025–2038. doi:10.1158/2767-9764.CRC-25-0243. PMC 12627933. PMID 41134690.
↑ Hallal R, de Toledo M, Tempé D, Berrahouane R, Zemiti S, Coënon L, et al. (January 2026). "Targeting SUMOylation Triggers IFN-β-dependent Activation of Patient and Allogenic NK Cells in Preclinical Models of Acute Myeloid Leukemia". Molecular Cancer Therapeutics. 25 (1): 125–139. doi:10.1158/1535-7163.MCT-25-0504. PMC 7618005. PMID 40661051.
↑ Köse H, Schneeweis C, Putze P, Contreras CT, Ferreiro L, Witte L, et al. (February 2026). "Targeting Mutual Dependence of Phosphatidylinositol-3-Kinase α/δ and Small Ubiquitin-Like Modifier Signaling in Pancreatic Cancer". Gastroenterology. 170 (2): 315–329. doi:10.1053/j.gastro.2025.08.018. PMID 41143762.

[1] Nakamura A, Grossman S, Song K, Xega K, Zhang Y, Cvet D, et al. (May 2022). "The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation". Blood. 139 (18): 2770–2781. doi:10.1182/blood.2021014267. PMC 11022956. PMID 35226739.

[2] Heynen GJ, Baumgartner F, Heider M, Patra U, Holz M, Braune J, et al. (February 2023). "SUMOylation inhibition overcomes proteasome inhibitor resistance in multiple myeloma". Blood Advances. 7 (4): 469–481. doi:10.1182/bloodadvances.2022007875. PMC 9979771. PMID 35917568.

[3] Lam V, Roleder C, Liu T, Bruss N, Best S, Wang X, et al. (September 2023). "T Cell-intrinsic Immunomodulatory Effects of TAK-981 (Subasumstat), a SUMO-activating Enzyme Inhibitor, in Chronic Lymphocytic Leukemia". Molecular Cancer Therapeutics. 22 (9): 1040–1051. doi:10.1158/1535-7163.MCT-22-0762. PMC 10525033. PMID 37420267.

[4] Gabellier L, De Toledo M, Chakraborty M, Akl D, Hallal R, Aqrouq M, et al. (January 2024). "SUMOylation inhibitor TAK-981 (subasumstat) synergizes with 5-azacytidine in preclinical models of acute myeloid leukemia". Haematologica. 109 (1): 98–114. doi:10.3324/haematol.2023.282704. PMC 10772526. PMID 37608777.

[5] Assouline SE, Mehta A, Hanel W, Doucet S, Johnston PB, Danilov A, et al. (November 2025). "Phase I/II Study of Subasumstat (TAK-981) in Combination With Rituximab in Relapsed/Refractory Non-Hodgkin Lymphoma". Clinical Lymphoma, Myeloma & Leukemia. 25 (11): 788–799.e11. doi:10.1016/j.clml.2025.04.020. PMID 40467383.

[6] Juric D, Anderson D, Dowlati A, Rodon J, Lugowska I, Mańdziuk S, et al. (November 2025). "A First-In-Human Study of the SUMOylation Inhibitor Subasumstat in Patients with Advanced/Metastatic Solid Tumors or Relapsed/Refractory Hematologic Malignancies". Cancer Research Communications. 5 (11): 2025–2038. doi:10.1158/2767-9764.CRC-25-0243. PMC 12627933. PMID 41134690.

[7] Hallal R, de Toledo M, Tempé D, Berrahouane R, Zemiti S, Coënon L, et al. (January 2026). "Targeting SUMOylation Triggers IFN-β-dependent Activation of Patient and Allogenic NK Cells in Preclinical Models of Acute Myeloid Leukemia". Molecular Cancer Therapeutics. 25 (1): 125–139. doi:10.1158/1535-7163.MCT-25-0504. PMC 7618005. PMID 40661051.

[8] Köse H, Schneeweis C, Putze P, Contreras CT, Ferreiro L, Witte L, et al. (February 2026). "Targeting Mutual Dependence of Phosphatidylinositol-3-Kinase α/δ and Small Ubiquitin-Like Modifier Signaling in Pancreatic Cancer". Gastroenterology. 170 (2): 315–329. doi:10.1053/j.gastro.2025.08.018. PMID 41143762.

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