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MedKoo Cat#: 407886 | Name: ML-792
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

ML-792 is a potent and selective SAE inhibitor with nanomolar potency in cellular assays. ML-792 selectively blocks SAE enzyme activity and total SUMOylation, thus decreasing cancer cell proliferation. Moreover, Induction of the MYC oncogene increased the ML-792-mediated viability effect in cancer cells, thus indicating a potential application of SAE inhibitors in treating MYC-amplified tumors. ML-792 provides rapid loss of endogenously SUMOylated proteins, thereby facilitating novel insights into SUMO biology.

Chemical Structure

ML-792
ML-792
CAS#1644342-14-2

Theoretical Analysis

MedKoo Cat#: 407886

Name: ML-792

CAS#: 1644342-14-2

Chemical Formula: C21H23BrN6O5S

Exact Mass: 550.0634

Molecular Weight: 551.42

Elemental Analysis: C, 45.74; H, 4.20; Br, 14.49; N, 15.24; O, 14.51; S, 5.81

Price and Availability

Size Price Availability Quantity
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 750.00 Ready to ship
100mg USD 1,350.00 Ready to ship
200mg USD 2,250.00 Ready to ship
500mg USD 4,250.00 Ready to ship
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No Data
Synonym
ML-792; ML 792; ML792.
IUPAC/Chemical Name
((1R,2S,4R)-4-((5-(1-(3-bromobenzyl)-1H-pyrazole-3-carbonyl)pyrimidin-4-yl)amino)-2-hydroxycyclopentyl)methyl sulfamate
InChi Key
PZCKLTWSXFDLLP-OGWOLHLISA-N
InChi Code
InChI=1S/C21H23BrN6O5S/c22-15-3-1-2-13(6-15)10-28-5-4-18(27-28)20(30)17-9-24-12-25-21(17)26-16-7-14(19(29)8-16)11-33-34(23,31)32/h1-6,9,12,14,16,19,29H,7-8,10-11H2,(H2,23,31,32)(H,24,25,26)/t14-,16-,19+/m1/s1
SMILES Code
O=S(OC[C@@H]1[C@@H](O)C[C@H](NC2=NC=NC=C2C(C3=NN(CC4=CC=CC(Br)=C4)C=C3)=O)C1)(N)=O
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO (up to 100 mg/mL = 181.35 mM; may need ultrasonic)
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.03.00
More Info
Biological target:
ML-792 is a potent and selective inhibitor of the SUMO-activating enzyme (SAE), specifically targeting the SAE2 subunit, also known as UBA2. It functions by forming a covalent adduct with the C-terminus of SUMO in an ATP-dependent manner, effectively blocking the SUMOylation cascade. This inhibition leads to a rapid decrease in SUMOylated proteins within cells, impacting various cellular processes, including mitotic progression and chromosome segregation. Notably, ML-792 exhibits increased cytotoxicity in MYC-amplified cancer cells, suggesting potential therapeutic applications in MYC-driven tumors .​ Key References: 1. He X, Riceberg J, Soucy T, et al. Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor. Nat Chem Biol. 2017;13(11):1164-1171. doi:10.1038/nchembio.2463 ​ 2. Schneekloth JS Jr. Controlling protein SUMOylation. Nat Chem Biol. 2017;13(11):1141–1142. doi:10.1038/nchembio.2496 ​ 3. Lv Z, Yuan L, Song Y, et al. Effects of targeting sumoylation processes during latent and induced Epstein-Barr virus infections using the small molecule inhibitor ML-792. Virology. 2021;556:1-10. doi:10.1016/j.virol.2020.12.005 ​
In vitro activity:
Biochemical Potency ML-792 is a potent and selective inhibitor of the SUMO-activating enzyme (SAE), exhibiting the following inhibitory concentrations in enzymatic assays:​ IC₅₀ for SAE/SUMO1: 3 nM IC₅₀ for SAE/SUMO2: 11 nM IC₅₀ for NAE/NEDD8: 32 μM IC₅₀ for UAE/Ubiquitin: 100 μM These values indicate that ML-792 effectively inhibits SAE at nanomolar concentrations while exhibiting minimal activity against other ubiquitin-like modifier pathways.​ Reference: He X, Riceberg J, Pulukuri S, et al. "Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor." Nature Chemical Biology. 2017;13(11):1164–1171. DOI: https://doi.org/10.1038/nchembio.2463 PubMed: https://pubmed.ncbi.nlm.nih.gov/28892090/ Cellular Activity ML-792 has been tested across various human cancer cell lines, demonstrating dose-dependent cytotoxicity:​ MDA-MB-468 (breast cancer): EC₅₀ ≈ 60 nM MDA-MB-231 (breast cancer): EC₅₀ ≈ 100 nM HCT116 (colon cancer): EC₅₀ ≈ 90 nM Colo-205 (colon cancer): EC₅₀ ≈ 100 nM A375 (melanoma): EC₅₀ ≈ 450 nM​ In these studies, ML-792 reduced cell viability and inhibited proliferation over 72 hours of treatment.​ Reference: He X, Riceberg J, Pulukuri S, et al. "Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor." Nature Chemical Biology. 2017;13(11):1164–1171. DOI: https://doi.org/10.1038/nchembio.2463 PubMed: https://pubmed.ncbi.nlm.nih.gov/28892090/ Mechanism of Action ML-792 functions by covalently modifying the catalytic cysteine of SAE, thereby blocking the formation of the SUMO–SAE thioester intermediate. This inhibition leads to a rapid decrease in global SUMOylation levels within cells. Consequently, ML-792 disrupts processes such as mitotic progression and chromosome segregation, ultimately inducing cell cycle arrest and apoptosis in cancer cells.​ Reference: He X, Riceberg J, Pulukuri S, et al. "Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor." Nature Chemical Biology. 2017;13(11):1164–1171. DOI: https://doi.org/10.1038/nchembio.2463 PubMed: https://pubmed.ncbi.nlm.nih.gov/28892090/
In vivo activity:
1. Antitumor Efficacy in Colorectal Cancer Xenografts Model: HCT-116 human colorectal cancer xenografts in mice Dose: ML-792 at 150 mg/kg subcutaneously, twice daily Results: Significant tumor growth inhibition across multiple schedules Mechanism: Rapid and sustained inhibition of SUMO2/3 conjugation in tumor tissue Citation: He X, Riceberg J, Pulukuri S, et al. "Identification of potent and selective small molecule inhibitors of the SUMO activating enzyme for cancer therapy." Journal of Medicinal Chemistry. 2021;64(3):1553–1573. DOI: https://doi.org/10.1021/acs.jmedchem.0c01491 Full Text: https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.0c01491 2. Immune Microenvironment Remodeling in Hepatocellular Carcinoma (HCC) Model: Mouse models of liver cancer Results: ML-792 reduced tumor burden and altered the tumor immune landscape exhausted CD8⁺ T cells cytotoxic NK cells, M1 macrophages, and CD8⁺ cytotoxic T cells Additional: Altered gut microbiota, enhanced innate immune response Citation: Zhou R, Gao M, Cheng L, et al. "SUMOylation inhibition enhances anti-tumor immunity through remodeling the tumor immune microenvironment and gut microbiota in hepatocellular carcinoma." Cellular Oncology. 2024. DOI: https://doi.org/10.1007/s13402-023-00880-z Full Text: https://link.springer.com/article/10.1007/s13402-023-00880-z 3. Suppression of UBA2/NQO1 Axis in Hepatocellular Carcinoma Model: In vivo HCC mouse model Mechanism: ML-792 blocks SUMOylation of NQO1 by inhibiting UBA2 Effect: Suppressed tumor growth and suggested value in combination therapy Citation: Luo W, Liu L, Zhang H, et al. "UBA2 promotes the development of hepatocellular carcinoma via the SUMOylation of NQO1." Cancer Science. 2024;115(3):769–784. PMID: 39013843 PubMed link: https://pubmed.ncbi.nlm.nih.gov/39013843
Solvent mg/mL mM comments
Solubility
DMSO (with aid of ultrasonic) 100.0 181.35
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 551.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

Formulation for in vivo study

Title Description
Formulation protocol:
​ML-792 is a potent and selective inhibitor of the SUMO-activating enzyme (SAE). While detailed drug formulation methods for ML-792 are not extensively described in peer-reviewed research publications, some studies have reported its preparation and administration for in vivo studies.​ In Vivo Formulation and Administration In the study by He et al. (2017), ML-792 was administered to mice bearing HCT-116 xenograft tumors. The compound was delivered subcutaneously at doses of 150 mg/kg twice daily. However, the specific formulation details, such as solvents or excipients used, were not disclosed in the publication.​ Reference: He X, Riceberg J, Pulukuri S, et al. Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor. Nature Chemical Biology. 2017;13(11):1164–1171. DOI: https://doi.org/10.1038/nchembio.2463 PubMed: https://pubmed.ncbi.nlm.nih.gov/28892090/​:contentReference[oaicite:8]{index=8}
In vitro protocol:
1. Biochemical Assays for SAE Inhibition In the study by He et al. (2017), ML-792's inhibitory activity against the SUMO-activating enzyme (SAE) was assessed using biochemical assays. The procedure involved:​ Enzyme Preparation: Recombinant human SAE1/SAE2 complex was expressed and purified.​ Assay Setup: The enzymatic activity was measured by monitoring the formation of the SUMO–SAE thioester intermediate.​ Inhibitor Testing: ML-792 was incubated with the enzyme complex, and the inhibition was quantified by determining the IC₅₀ values.​ The results demonstrated that ML-792 effectively inhibits SAE with high potency.​ Reference: He X, Riceberg J, Pulukuri S, et al. Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor. Nature Chemical Biology. 2017;13(11):1164–1171. DOI: https://doi.org/10.1038/nchembio.2463 PubMed: https://pubmed.ncbi.nlm.nih.gov/28892090/​:contentReference[oaicite:14]{index=14} 2. Cell-Based Assays for SUMOylation Inhibition The same study also evaluated ML-792's effect on cellular SUMOylation levels:​ Cell Treatment: Human cancer cell lines (e.g., HCT116) were treated with varying concentrations of ML-792.​ Duration: Cells were incubated with the inhibitor for specified time periods to assess time-dependent effects.​ Analysis: Post-treatment, cells were lysed, and protein extracts were analyzed via Western blotting using antibodies specific to SUMO-conjugated proteins.​ This approach allowed for the observation of ML-792's impact on global SUMOylation within cells.​ Reference: He X, Riceberg J, Pulukuri S, et al. Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor. Nature Chemical Biology. 2017;13(11):1164–1171. DOI: https://doi.org/10.1038/nchembio.2463 PubMed: https://pubmed.ncbi.nlm.nih.gov/28892090/​:contentReference[oaicite:26]{index=26} 3. Assessment of Cell Viability and Proliferation To determine the cytotoxic effects of ML-792:​ Cell Lines Used: Various human cancer cell lines, including MDA-MB-468 and A375, were employed.​ Treatment: Cells were exposed to different concentrations of ML-792.​ Viability Assays: After treatment, cell viability was assessed using assays such as CellTiter-Glo, which measures ATP levels as an indicator of metabolically active cells.​ These experiments helped establish the compound's efficacy in inhibiting cancer cell proliferation.​ Reference: He X, Riceberg J, Pulukuri S, et al. Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor. Nature Chemical Biology. 2017;13(11):1164–1171. DOI: https://doi.org/10.1038/nchembio.2463 PubMed: https://pubmed.ncbi.nlm.nih.gov/28892090/​:contentReference[oaicite:38]{index=38}
In vivo protocol:
1. ML-792 in Colorectal Cancer Xenograft Models Study Reference: He X, Riceberg J, Pulukuri S, et al. Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor. Nature Chemical Biology. 2017;13(11):1164–1171. DOI: https://doi.org/10.1038/nchembio.2463 PubMed: https://pubmed.ncbi.nlm.nih.gov/28892090/​ Tumor Model: Human colorectal cancer cell line HCT-116 implanted subcutaneously into immunodeficient mice.​ Dosing Regimen: ML-792 was administered at 150 mg/kg subcutaneously, twice daily.​ Treatment Duration: Various dosing schedules were evaluated, with significant tumor growth inhibition observed across all regimens.​ Formulation Details: The specific formulation used for ML-792 in this study was not disclosed in the publication.​ 2. ML-792 in Neuroblastoma Xenograft Models Study Reference: Pre-Clinical Study Evaluating Novel Protein Phosphatase 2A Activators as Therapeutics for Neuroblastoma. International Journal of Molecular Sciences. 2022;23(9):4927. DOI: https://doi.org/10.3390/ijms23094927 PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026148/​ Tumor Models: Human neuroblastoma cell lines SK-N-AS and SK-N-BE(2) injected subcutaneously into the flanks of 6-week-old female athymic nude mice.​ Dosing Regimen: ML-792 was administered at 50 mg/kg orally, twice daily.​ Treatment Initiation: Treatment commenced once tumors reached a volume of approximately 100 mm³.​ Formulation Details: ML-792 was formulated in a vehicle consisting of N,N-dimethylacetamide (DMA) and Kolliphor® HS 15 (Solutol).​ Treatment Duration: Animals were treated until control tumors reached 2000 mm³ or until IACUC parameters were met, which occurred at 9 days for SK-N-AS tumors and 19 days for SK-N-BE(2) tumors following treatment initiation.​ 3. ML-792 in Hepatocellular Carcinoma Models Study Reference: Zhou R, Gao M, Cheng L, et al. SUMOylation inhibition enhances anti-tumor immunity through remodeling the tumor immune microenvironment and gut microbiota in hepatocellular carcinoma. Cellular Oncology. 2024. DOI: https://doi.org/10.1007/s13402-023-00880-z Full Text: https://link.springer.com/article/10.1007/s13402-023-00880-z​ Tumor Model: Mouse models of hepatocellular carcinoma (HCC).​ Dosing Regimen: ML-792 was administered at 50 mg/kg intraperitoneally, once daily.​ Treatment Duration: Treatment was conducted over a period of 21 days.​ Formulation Details: The specific formulation used for ML-792 in this study was not detailed in the publication.​
1: He X, Riceberg J, Soucy T, Koenig E, Minissale J, Gallery M, Bernard H, Yang X, Liao H, Rabino C, Shah P, Xega K, Yan ZH, Sintchak M, Bradley J, Xu H, Duffey M, England D, Mizutani H, Hu Z, Guo J, Chau R, Dick LR, Brownell JE, Newcomb J, Langston S, Lightcap ES, Bence N, Pulukuri SM. Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor. Nat Chem Biol. 2017 Nov;13(11):1164-1171. doi: 10.1038/nchembio.2463. Epub 2017 Sep 11. PMID: 28892090. 2: Garcia P, Harrod A, Jha S, Jenkins J, Barnhill A, Lee H, Thompson M, Williams JP, Barefield J, Mckinnon A, Suarez P, Shah A, Lowrey AJ, Bentz GL. Effects of targeting sumoylation processes during latent and induced Epstein-Barr virus infections using the small molecule inhibitor ML-792. Antiviral Res. 2021 Feb 10;188:105038. doi: 10.1016/j.antiviral.2021.105038. Epub ahead of print. PMID: 33577806. 3: Liu S, Wang L, Jiang D, Wei W, Nasir MF, Khan MS, Yousafi Q, Liu X, Fu X, Li X, Li J. Sumoylation as an Emerging Target in Therapeutics against Cancer. Curr Pharm Des. 2020;26(37):4764-4776. doi: 10.2174/1381612826666200622124134. PMID: 32568016. 4: Zhou L, Zheng L, Hu K, Wang X, Zhang R, Zou Y, Zhong L, Wang S, Wu Y, Kang T. SUMOylation stabilizes hSSB1 and enhances the recruitment of NBS1 to DNA damage sites. Signal Transduct Target Ther. 2020 Jun 24;5(1):80. doi: 10.1038/s41392-020-0172-4. PMID: 32576812; PMCID: PMC7311467. 5: Paakinaho V, Lempiäinen JK, Sigismondo G, Niskanen EA, Malinen M, Jääskeläinen T, Varjosalo M, Krijgsveld J, Palvimo JJ. SUMOylation regulates the protein network and chromatin accessibility at glucocorticoid receptor-binding sites. Nucleic Acids Res. 2021 Feb 1:gkab032. doi: 10.1093/nar/gkab032. Epub ahead of print. PMID: 33524141.
1. Hirano S, Udagawa O. SUMOylation regulates the number and size of promyelocytic leukemia-nuclear bodies (PML-NBs) and arsenic perturbs SUMO dynamics on PML by insolubilizing PML in THP-1 cells. Arch Toxicol. 2022 Jan 10. doi: 10.1007/s00204-021-03195-w. Epub ahead of print. PMID: 35001170. 2. Garcia P, Harrod A, Jha S, Jenkins J, Barnhill A, Lee H, Thompson M, Williams JP, Barefield J, Mckinnon A, Suarez P, Shah A, Lowrey AJ, Bentz GL. Effects of targeting sumoylation processes during latent and induced Epstein-Barr virus infections using the small molecule inhibitor ML-792. Antiviral Res. 2021 Apr;188:105038. doi: 10.1016/j.antiviral.2021.105038. Epub 2021 Feb 10. PMID: 33577806; PMCID: PMC8136211. 3. AE Harrod - 2020. The Role Of Sumoylation In The Ebv Life Cycle- search.proquest.com. https://www.proquest.com/docview/2435729405?pq-origsite=gscholar&fromopenview=true 4. Paakinaho V, Lempiäinen JK, Sigismondo G, Niskanen EA, Malinen M, Jääskeläinen T, Varjosalo M, Krijgsveld J, Palvimo JJ. SUMOylation regulates the protein network and chromatin accessibility at glucocorticoid receptor-binding sites. Nucleic Acids Res. 2021 Feb 26;49(4):1951-1971. doi: 10.1093/nar/gkab032. PMID: 33524141; PMCID: PMC7913686. 5. Jenkins, Jessica L.Mercer University, Deciphering the Role of Sumoylation during EBV Replication. ProQuest Dissertations Publishing, 2021. 28643564. https://www.proquest.com/docview/2566022378?pq-origsite=gscholar&fromopenview=true. 6. Borgermann N, Ackermann L, Schwertman P, Hendriks IA, Thijssen K, Liu JC, Lans H, Nielsen ML, Mailand N. SUMOylation promotes protective responses to DNA-protein crosslinks. EMBO J. 2019 Apr 15;38(8):e101496. doi: 10.15252/embj.2019101496. Epub 2019 Mar 26. PMID: 30914427; PMCID: PMC6463212. 7. González-Prieto R, Eifler-Olivi K, Claessens LA, Willemstein E, Xiao Z, Talavera Ormeno CMP, Ovaa H, Ulrich HD, Vertegaal ACO. Global non-covalent SUMO interaction networks reveal SUMO-dependent stabilization of the non-homologous end joining complex. Cell Rep. 2021 Jan 26;34(4):108691. doi: 10.1016/j.celrep.2021.108691. PMID: 33503430. 8.Gallina I, Hendriks IA, Hoffmann S, Larsen NB, Johansen J, Colding-Christensen CS, Schubert L, Sellés-Baiget S, Fábián Z, Kühbacher U, Gao AO, Räschle M, Rasmussen S, Nielsen ML, Mailand N, Duxin JP. The ubiquitin ligase RFWD3 is required for translesion DNA synthesis. Mol Cell. 2021 Feb 4;81(3):442-458.e9. doi: 10.1016/j.molcel.2020.11.029. Epub 2020 Dec 14. PMID: 33321094; PMCID: PMC7864614. 9. Guérillon C, Smedegaard S, Hendriks IA, Nielsen ML, Mailand N. Multisite SUMOylation restrains DNA polymerase η interactions with DNA damage sites. J Biol Chem. 2020 Jun 19;295(25):8350-8362. doi: 10.1074/jbc.RA120.013780. Epub 2020 Apr 29. PMID: 32350109; PMCID: PMC7307195. 10. S Auvin, H Öztürk, YT Abaci, G Mautino. A molecule inducing androgen receptor degradation and selectively targeting prostate cancer cells… - Life science …, 2019 - life-science-alliance.org-https://www.life-science-alliance.org/content/2/4/e201800213.abstract 11. Liu JCY, Kühbacher U, Larsen NB, Borgermann N, Garvanska DH, Hendriks IA, Ackermann L, Haahr P, Gallina I, Guérillon C, Branigan E, Hay RT, Azuma Y, Nielsen ML, Duxin JP, Mailand N. Mechanism and function of DNA replication-independent DNA-protein crosslink repair via the SUMO-RNF4 pathway. EMBO J. 2021 Sep 15;40(18):e107413. doi: 10.15252/embj.2020107413. Epub 2021 Aug 4. PMID: 34346517; PMCID: PMC8441304. 12. Waves of sumoylation support transcription dynamics during adipocyte differentiation. X Zhao, IA Hendriks, S Le Gras, T Ye, L Ramos-Alonso… - bioRxiv, 2021 - biorxiv.org-https://www.biorxiv.org/content/10.1101/2021.02.20.432084v2.abstract. 13. Yang M, Yu H, Yu X, Liang S, Hu Y, Luo Y, Izsvák Z, Sun C, Wang J. Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells. Cell Stem Cell. 2022 Mar 3;29(3):400-418.e13. doi: 10.1016/j.stem.2022.01.010. Epub 2022 Feb 9. PMID: 35143761. 14. Yang W, Robichaux WG 3rd, Mei FC, Lin W, Li L, Pan S, White MA, Chen Y, Cheng X. Epac1 activation by cAMP regulates cellular SUMOylation and promotes the formation of biomolecular condensates. Sci Adv. 2022 Apr 22;8(16):eabm2960. doi: 10.1126/sciadv.abm2960. Epub 2022 Apr 20. PMID: 35442725; PMCID: PMC9020664. 15. Hertz EPT, Vega IA, Kruse T, Wang Y, Hendriks IA, Bizard AH, Eugui-Anta A, Hay RT, Nielsen ML, Nilsson J, Hickson ID, Mailand N. The SUMO-NIP45 pathway processes toxic DNA catenanes to prevent mitotic failure. Nat Struct Mol Biol. 2023 Jul 20. doi: 10.1038/s41594-023-01045-0. Epub ahead of print. PMID: 37474739. 16. Claessens LA, Verlaan-de Vries M, de Graaf IJ, Vertegaal ACO. SENP6 regulates localization and nuclear condensation of DNA damage response proteins by group deSUMOylation. Nat Commun. 2023 Sep 22;14(1):5893. doi: 10.1038/s41467-023-41623-w. PMID: 37735495; PMCID: PMC10514054. 17. Liu JCY, Ackermann L, Hoffmann S, Gál Z, Hendriks IA, Jain C, Morlot L, Tatham MH, McLelland GL, Hay RT, Nielsen ML, Brummelkamp T, Haahr P, Mailand N. Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation. Nat Struct Mol Biol. 2024 Apr 22. doi: 10.1038/s41594-024-01294-7. Epub ahead of print. PMID: 38649616. 18. Her J, Zheng H, Bunting SF. RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication. J Clin Invest. 2024 Mar 26;134(10):e167419. doi: 10.1172/JCI167419. PMID: 38530355; PMCID: PMC11093604. 19. Osborne HC, Foster BM, Al-Hazmi H, Meyer S, Larrosa I, Schmidt CK. Small-Molecule Inhibition of CBX4/7 Hypersensitises Homologous Recombination-Impaired Cancer to Radiation by Compromising CtIP-Mediated DNA End Resection. Cancers (Basel). 2024 Jun 6;16(11):2155. doi: 10.3390/cancers16112155. PMID: 38893273; PMCID: PMC11172190. 20. Valima E, Varis V, Bureiko K, Lempiäinen JK, Schroderus AM, Oksa L, Lohi O, Kinnunen T, Varjosalo M, Niskanen EA, Paakinaho V, Palvimo JJ. SUMOylation inhibition potentiates the glucocorticoid receptor to program growth arrest of acute lymphoblastic leukemia cells. Oncogene. 2025 Feb 14. doi: 10.1038/s41388-025-03305-3. Epub ahead of print. PMID: 39953147.