GLPBio

ML-323

Catalog No.: GC17635Purity:>99.50%
COASDSData Sheet
ML-323 ist ein reversibler, potenter USP1-UAF1-Inhibitor mit einem IC50-Wert von 76 nM in einem Ub-Rho-Assay. Die gemessene Hemmkonstante von ML-323 fÜr das freie Enzym (Ki) betrÄgt 68 nM.

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ML-323
Cas No.: 1572414-83-5
10mM (in 1mL DMSO)In Stock
$58.00
1
1mgIn Stock
$24.00
1
5mgIn Stock
$52.00
1
10mgIn Stock
$84.00
1
25mgIn Stock
$168.00
1
50mgIn Stock
$252.00
1
100mgIn Stock
$378.00
1
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Zitate (Citations)

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    187(9):2288-2304 (2024)
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    183(7):1867-1883 (2020)
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Beschreibung (Description)

ML-323 is a highly reversible and highly effective selective inhibitor of USP1-UAF1 with an IC50 value of 76nM. The Ki value of ML-323 for free enzymes is 68nM. USP1-UAF1 is closely related to the DNA damage response and can be used for the study of anti-tumor drug resistance [1]. ML-323 has anti-cancer activity against various cancers [2-3].

In vitro, in the Ub-Rho experiment, ML-323 (0.08-114μM; 1-2h) exhibited dose-dependent inhibition of USP1-UAF1 with an IC50 value of 76nM [1]. ML-323 (0-200μM; 48h) inhibited the growth of HCCLM3 and SMMC-7721 HCC cells and the formation of colonies in a dose-dependent manner [4]. ML-323 (0-400nM; 0, 4, 8 and 16h) could down-regulate the expression of USP1 in colorectal cancer cells in a dose-dependent and time-dependent manner [5].

In vivo, the injection treatment of ML-323 (10mg/kg; 7 days) significantly increased the body weight of mice with colitis models and decreased the MPO activity in colonic tissues and ulcer areas, and had a significant inhibitory effect on the levels of inflammatory markers (TNF-α, IL-6, IL-17 and IL-1β) in the colonic tissues of colitis mice [6]. ML-323 (25 and 50mg/kg/day; oral; twice a week for 8 weeks) treatment significantly reduced the body weight of mice fed a high-fat diet (HFD), improved insulin and glucose sensitivity, and significantly decreased the fat content and size of adipocytes in white adipose tissue, reduced lipid accumulation, triglycerides, free fatty acids and macrophage infiltration in the liver of the mice [7].

References:
[1] Liang Q, Dexheimer T S, Zhang P, et al. A selective USP1–UAF1 inhibitor links deubiquitination to DNA damage responses[J]. Nature chemical biology, 2014, 10(4): 298-304.
[2] Sun Y, Sha B, Huang W, et al. ML323, a USP1 inhibitor triggers cell cycle arrest, apoptosis and autophagy in esophageal squamous cell carcinoma cells[J]. Apoptosis, 2022, 27(7): 545-560.
[3] Song B, Jiang Y, Jiang Y, et al. ML323 suppresses the progression of ovarian cancer via regulating USP1-mediated cell cycle[J]. Frontiers in Genetics, 2022, 13: 917481. 
[4] Wang L, Hu T, Shen Z, et al. Inhibition of USP1 activates ER stress through Ubi-protein aggregation to induce autophagy and apoptosis in HCC[J]. Cell Death & Disease, 2022, 13(11): 951.
[5] Xu X, Mei X, Han K, et al. The deubiquitinating enzyme USP1 is auto-ubiquitinated and destabilized by ML323 in colorectal cancer cells[J]. Eurasian J Med Oncol, 2023, 7: 174-179.
[6] Lai Y, Liu J, Hu X, et al. N6-methyladenosine (m6A)-forming enzyme METTL3 controls UAF1 stability to promote inflammation in a model of colitis by stimulating NLRP3[J]. Scientific Reports, 2025, 15(1): 5876. 
[7] Kim M S, Baek J H, Lee J A, et al. Deubiquitinase USP1 enhances CCAAT/enhancer-binding protein beta (C/EBPβ) stability and accelerates adipogenesis and lipid accumulation[J]. Cell Death & Disease, 2023, 14(11): 776.

Protokoll (Protocol)

Kinase experiment [1]:

Preparation Method

To determine the IC50 of ML323 in inhibiting USP1-UAF1, the inhibitor was added at seven different concentrations to the assay containing 150nM USP1-UAF1 and 3μM K63-linked diubiquitin or 300nM USP1-UAF1 and 3μM Ub-PCNA in a buffer containing 50mM HEPES (pH 7.8), 0.1mg ml−1 BSA, 0.5mM EDTA and 1mM or 5mM DTT for 1–2 h at 37°C. The reaction was quenched by the addition of Laemmli sample buffer. In the in vitro ML-323 selectivity test, six different concentrations (0.08–114μM) of ML-323 and 3μM K63-linked diubiquitin were incubated individually with 7.5nM USP7, 30nM USP2, 15nM USP5, 255nM USP8, 100nM USP11, 600nM USP21 and 600nM USP46-UAF1.

Reaction Conditions

0.08-114μM; 1-2h

Applications

In the Ub-Rho assay, ML-323 exhibited dose-dependent inhibition of USP1-UAF1, with its IC50 value being 76nM. ML323 showed no significant inhibitory effect on other proteases and kinases.

Cell experiment [2]:

Cell lines

HCC cell lines

Preparation Method

HCC cell lines HCCLM3, HepG2, Huh7, and SMMC-7721 were uniformly seeded in a 96-well plate (3 × 103 cells/well) and treated with ML-323 or DMSO (0.1%) for 48h. Cell viability was determined using a cell-counting-kit (CCK)-8 according to the manufacturer’s protocol. For the colony formation assay, 500 cells were seeded into a 6-well plate in triplicate, treated with DMSO or ML-323, and incubated for 10d. The colonies were treated with 4% paraformaldehyde and crystal violet, then counted.

Reaction Conditions

0-200μM; 48h

Applications

ML-323 inhibited the growth of HCCLM3 and SMMC-7721 HCC cells in a dose-dependent manner, and also inhibited colony formation.
Animal experiment [3]:

Animal models

C57BL/6 mice (colitis models)

Preparation Method

Male C57BL/6 mice (4-5 weeks, 17–19g) were purchased from Animal Experimental Center of Guangdong Medical University. Colitis was induced by administering 2.0% dextran sulfate sodium (DSS) in the drinking water for 7 days. Mice were provided with a standard diet and water ad libitum. UAF1 inhibitor (10mg/kg/day for 7 days of ML-323) was injected. Anesthesia was induced with 50mg/kg pentobarbital sodium, and mice were euthanized by cervical dislocation. Colon tissues, RAW264.7 macrophages, and serum samples were extracted.

Dosage form

10mg/kg/day for 7 days; inject

Applications

Treatment with ML-323 significantly increased the body weight of mice and reduced the MPO activity in colonic tissues and ulcer areas. It also had a significant inhibitory effect on the levels of inflammatory markers (TNF-α, IL-6, IL-17 and IL-1β) in the colonic tissues of colitis mice.

References:
[1] Liang Q, Dexheimer T S, Zhang P, et al. A selective USP1–UAF1 inhibitor links deubiquitination to DNA damage responses[J]. Nature chemical biology, 2014, 10(4): 298-304.
[2] Wang L, Hu T, Shen Z, et al. Inhibition of USP1 activates ER stress through Ubi-protein aggregation to induce autophagy and apoptosis in HCC[J]. Cell Death & Disease, 2022, 13(11): 951.
[3] Lai Y, Liu J, Hu X, et al. N6-methyladenosine (m6A)-forming enzyme METTL3 controls UAF1 stability to promote inflammation in a model of colitis by stimulating NLRP3[J]. Scientific Reports, 2025, 15(1): 5876.

Produktdokumente (Product Documents)

Purity:>99.50%Appearance:A solid
COASDSData Sheet

Chemische Eigenschaften (Chemical Properties)

CAS-Nr.
1572414-83-5
Chemischer Name
(E)-1-(4-(1H-1,2,3-triazol-1-yl)phenyl)-N-(2-(2-isopropylphenyl)-5-methylpyrimidin-4(3H)-ylidene)methanamine
SMILES
CC(C1=CC=CC=C1C2=NC=C(/C(N2)=N\CC3=CC=C(N4C=CN=N4)C=C3)C)C
Summenformel
C23H24N6
Molekulargewicht
384.48
Löslichkeit
≥ 15.05mg/mL in DMSO
Lagerung
Store at -20°C
Allgemeine Hinweise
Wählen Sie anhand der Löslichkeitsdaten des Produkts ein geeignetes Lösungsmittel. Aliquotieren Sie die Stammlösung nach der Herstellung, um wiederholte Gefrier-Auftau-Zyklen zu vermeiden.
Verwenden Sie Stammlösungen bei Lagerung bei -80°C innerhalb von 6 Monaten bzw. bei -20°C innerhalb von 1 Monat.
Zur Verbesserung der Löslichkeit das Röhrchen auf 37°C erwärmen und für eine angemessene Dauer beschallen.
Versandbedingungen
Evaluierungsmuster werden mit Kühlakkus versandt. Andere verfügbare Größen werden bei Raumtemperatur oder auf Anfrage mit Kühlakkus versandt.

Rechner (Calculators)Molarität / Verdünnung / Molekulargewicht / Einheitenumrechnung / In-vivo-Formulierung / Löslichkeit

g/mol

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