ML-792
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MedKoo CAT#: 407886

CAS#: 1644342-14-2

Description: 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

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ML-792
CAS# 1644342-14-2
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 407886
Name: ML-792
CAS#: 1644342-14-2
Chemical Formula: C21H23BrN6O5S
Exact Mass: 550.06
Molecular Weight: 551.416
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 Ready to ship
10mg USD 250 Ready to ship
25mg USD 450 Ready to ship
50mg USD 750 Ready to ship
100mg USD 1350 Ready to ship
200mg USD 2250 Ready to ship
500mg USD 4250 Ready to ship
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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: SAE/SUMO1 and SAE/SUMO2 in enzymatic assays (IC50 values of 3 and 11 nM, respectively)
In vitro activity: ML-792 was found to be a potent inhibitor of SAE in ATP–inorganic pyrophosphate (PPi) exchange assays (Fig. 1b). The half-maximal inhibitory concentration (IC50) was 0.003 μM or 0.011 μM when SUMO1 or SUMO2 was used as the ubiquitin-like protein (UBL), respectively. ML-792 was selective for inhibition of SAE activity, as compared with the closely related E1 enzymes NAE (IC50 =32 μM) and ubiquitin-activating enzyme (UAE) (IC50 > 100 μM). In addition, ML-792 was screened against a panel of 366 ATP-using enzymes and did not demonstrate significant inhibition at a 1 μM concentration. ML-792 is a potent and selective SAE inhibitor in multiple cancer cell lines that does not affect the activity of other E1s. The reported UBA2-knockdown synthetic-lethal effect with MYC overexpression and suggested a potential application for ML-792 in treating MYC-amplified tumors. [Reference: Nature Chemical Biology volume 13, pages1164–1171(2017)]
In vivo activity: The knocking out UBC9 with two highly efficient lenti-CRISPR sgRNAs did not affect the apoptosis rate in the short term but increased the apoptosis of cancer cells treated with etoposide (Fig. (Fig.6b).6b). Apoptosis was also enhanced in cancer cells when treated with a combination of 2-D08 or ML-792 with etoposide compared with the treatment of etoposide alone, while 2-D08 or ML-792 treatments administered alone only slightly affected apoptosis (Fig. 6c, d). Furthermore, as shown in Fig. 6e–g, the combination of etoposide and 2-D08 sensitized tumors in nude mice to etoposide. These results indicate that targeting SUMOylation enhances the sensitivity of cancer cells to DNA damage agents. [reference: Signal Transduct Target Ther. 2020; 5: 80., web page: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311467/]

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO (with aid of ultrasonic) 100.0 181.35

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 protocol: Nat Chem Biol . 2017 Nov;13(11):1164-1171. doi: 10.1038/nchembio.2463. Epub 2017 Sep 11
In vitro protocol: Cell survival assays HeLa cells were infected with lentivirus encoding the hSSB1 CRISPR-Cas9 sequence and then reinfected with pTETON-hSSB1/DM or an empty vector virus. The WT/DM were same sense mutated to be resistant to CRISPR-Cas9 cleavage, after. After puromycin selection for 7 days, the cells were treated with doxycycline (5 ng/ml) to induce the expression of WT/DM. Then, 500 cells were seeded into six-well plates for 24 h, and the cells were irradiated at 2, 4, or 6 Gy as indicated. The cells were then incubated for 14 days. The resulting colonies were fixed and stained with crystal violet. [Reference: Signal Transduct Target Ther. 2020; 5: 80. Web page: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311467/] Apoptosis assay U2OS cells with stably knocked out UBC9 were seeded on six-well plates for 24 h, and then treated with etoposide (20 µM) for 48 h to induce apoptosis. Then, the cells were collected by trypsin without EDTA, washed with PBS, subjected to annexin V-FITC, and propidium iodide staining according to the manufacturer’s recommendations (KeyGen Biotech), and analyzed by flow cytometry. HCT116 cells were treated with 50 µM etoposide, 200 µM 2-D08, 10 µM ML-792, or a combination of these drugs, as indicated, for 24 h, and then the cells were collected and analyzed by flow cytometry. [Reference: Signal Transduct Target Ther. 2020; 5: 80. Web page: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311467/]
In vivo protocol: Xenograft tumor model Animal studies were approved by the Animal Research Committee of Sun Yat-sen University Cancer Center. Male athymic BALB/C nude mice (4 weeks old) were obtained from Vital River Laboratory Animal Technology (Beijing, China). Briefly, 4 × 106 HCT116 cells were resuspended in 0.1 ml of PBS and subcutaneously injected into the flanks of the mice. After 8 days of the injection, the mice were treated intraperitoneally with 2-D08 (5 mg/kg) and/or etoposide (10 mg/kg) every 2 days for 10 days. The solvents used were 5% DMSO, 40% PEG300, and 55% normal saline. Tumor volumes were measured every 2 days and were calculated using the formula V = 0.5 × length × width2. All mice were sacrificed 18 days after injection, and the xenograft tumors were isolated, photographed, and weighed. [Reference: Signal Transduct Target Ther. 2020; 5: 80. Web page: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311467/]

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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.

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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.

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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.