Art. -Nr.: HY-17543

ML-323

Name: ML-323
Brand: MedChemExpress
SKU: HY-17543
Price: 66.00 USD
Availability: InStock
Rating: 5 (19 reviews)

19 Cited Publications

Kundenbewertung

Based on 19 publication(s) in Google Scholar

ML-323 is a reversible, potent USP1-UAF1 inhibitor with IC₅₀ of 76 nM in a Ub-Rho assay. The measured inhibition constants of ML-323 for the free enzyme (K_i) is 68 nM.

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Reinheit: 99.51%
CAS. Nr.: 1572414-83-5
Formel: C₂₃H₂₄N₆
Molecular Weight:384.48

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months

ML-323 Chemical Structure

CAS. Nr.: 1572414-83-5

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
Chemical Information
Publications (19)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

ML-323 is a reversible, potent USP1-UAF1 inhibitor with IC₅₀ of 76 nM in a Ub-Rho assay. The measured inhibition constants of ML-323 for the free enzyme (K_i) is 68 nM.

IC₅₀ & Target

IC50: 76 nM (USP1-UAF1, in Ub-Rho assay)^[1]
Ki: 68 nM (USP1-UAF1)^[1]

Alle Deubiquitinase Isoform-spezifische Produkte anzeigen :

In Vitro

ML-323 (ML323) is a highly potent inhibitor of the USP1-UAF1 deubiquitinase complex with excellent selectivity against human DUBs, deSUMOylase, deneddylase and unrelated proteases. ML-323 is a potent USP1-UAF1 inhibitor with IC50 values of 76 nM in a ubiquitin-rhodamine (Ub-Rho) assay and 174 nM and 820 nM in orthogonal gel-based assays using K63-linked diubiquitin (di-Ub) and monoubiquitinated PCNA (Ub-PCNA) as substrates, respectively. ML-323 probably exerts its inhibitory effect through an allosteric mechanism. The measured inhibition constants of ML-323 for the free enzyme (K_i) and the enzyme-substrate complex (K’_i) are 68 nM and 183 nM. Besides, ML-323 potentiates Cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells^[1]. ML-323 (ML323), a probe molecule that displays reversible, nanomolar inhibitory activity and excellent selectivity toward USP1/UAF1. In addition, ML-323 potentiates the cytotoxicity of Cisplatin and increases endogenous monoubiquitination levels of both PCNA and FANCD2, two known cellular targets of USP1/UAF1^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Chemical Information

CAS. Nr. 1572414-83-5
Appearance Solid
Molecular Weight 384.48
Formel C₂₃H₂₄N₆
Color White to off-white
SMILES

CC1=CN=C(C2=C(C(C)C)C=CC=C2)N=C1NCC3=CC=C(N4N=NC=C4)C=C3
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Publications (19)

All Bio/Physico-chemical AssayWBCell Proliferation/Viability Assay

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Journal Impact Factor

Nat Commun

Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]

2026 Feb 12;17(1):1214. PMID: 41680175
Nat Commun

USP2 inhibition unleashes CD47-restrained phagocytosis and enhances anti-tumor immunity. [Abstract]

2025 May 16;16(1):4564. PMID: 40379682
Nat Commun

USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy. [Abstract]

2022 Mar 31;13(1):1700. PMID: 35361799
Redox Biol

USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers. [Abstract]

2026 May:92:104086. PMID: 41844497
Nucleic Acids Res

USP1-dependent nucleolytic expansion of PRIMPOL-generated nascent DNA strand discontinuities during replication stress. [Abstract]

2024 Mar 21;52(5):2340-2354. PMID: 38180818

ML-323 purchased from MedChemExpress. Usage Cited in: Nucleic Acids Res. 2024 Mar 21;52(5):2340-2354. [Abstract]

ML-323 (20 μM; 2.5 h) suppressesed the binding of MRE11 and EXO1 to nascent DNA in HeLa PRIMPOL-overexpressing cells.

ML-323 purchased from MedChemExpress. Usage Cited in: Nucleic Acids Res. 2024 Mar 21;52(5):2340-2354. [Abstract]

ML-323 (10-30 μM; 3.5 h) suppressesed the accumulation of replication-associated ssDNA gaps induced by exposure to 150μM cisplatin or 0.4mM HU in U2OS and HeLa PRIMPOL-overexpressing cells.

ML-323 purchased from MedChemExpress. Usage Cited in: Nucleic Acids Res. 2024 Mar 21;52(5):2340-2354. [Abstract]

ML-323 (20 μM; 4.5 h) suppressesed the accumulation of replication-associated ssDNA gaps induced by exposure to 0.4 mM HU in HeLa PRIMPOL-overexpressing cells.
Cell Death Dis

Inhibition of USP1 activates ER stress through Ubi-protein aggregation to induce autophagy and apoptosis in HCC. [Abstract]

2022 Nov 10;13(11):951. PMID: 36357365
J Immunother Cancer

CD47 destabilization via manipulating the SPOP-USP2 axis augments macrophage phagocytosis and cancer immunotherapy. [Abstract]

2026 Jan 14;14(1):e013498. PMID: 41534899
Int J Biol Sci

USP1 inhibition suppresses the progression of osteosarcoma via destabilizing TAZ. [Abstract]

2022 May 1;18(8):3122-3136. PMID: 35637948

ML-323 purchased from MedChemExpress. Usage Cited in: Int J Biol Sci. 2022 May 1;18(8):3122-3136. [Abstract]

ML-323 (8-32 μM; 48 h) reduced the expression of TAZ and downstream genes in Hippo signaling pathway in 143B and HOS cells.

ML-323 purchased from MedChemExpress. Usage Cited in: Int J Biol Sci. 2022 May 1;18(8):3122-3136. [Abstract]

ML-323 (8-32 μM; 7-14 d) weakened the ability of OS cells in forming colonies.
Cell Chem Biol

Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2. [Abstract]

2021 Jun 17;28(6):855-865.e9. PMID: 33979649
EMBO J

Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway. [Abstract]

2015 May 12;34(10):1385-98. PMID: 25862789
Cell Prolif

Comprehensive analysis of ubiquitin-specific protease 1 reveals its importance in hepatocellular carcinoma. [Abstract]

2020 Oct;53(10):e12908. PMID: 32951278

ML-323 purchased from MedChemExpress. Usage Cited in: Cell Prolif. 2020 Oct;53(10):e12908. [Abstract]

ML-323 (50 μM; 24 hours) treatment down-regulates USP1 and WDR48 in MHCC97H and SK-Hep-1 cells. And also decreases the protein expression of PCNA, cyclin D1 and cyclin E1.
J Med Chem

Discovery of Potent OTUB1/USP8 Dual Inhibitors Targeting Proteostasis in Non-Small-Cell Lung Cancer. [Abstract]

2022 Oct 27;65(20):13645-13659. PMID: 36221183
Mol Cancer Ther

2026 Jul 15:10.1158/1535-7163.MCT-26-0182. PMID: 42456172
Sci Rep

N6-methyladenosine (m6A)-forming enzyme METTL3 controls UAF1 stability to promote inflammation in a model of colitis by stimulating NLRP3. [Abstract]

2025 Feb 18;15(1):5876. PMID: 39966502
J Neurosci

USP1/UAF1-stabilized METTL3 promotes reactive astrogliosis and improves functional recovery after spinal cord injury through m6A modification of YAP1 mRNA. [Abstract]

2023 Mar 1;43(9):1456-1474. PMID: 36653190
Viruses

Inhibitors of the Ubiquitin-Mediated Signaling Pathway Exhibit Broad-Spectrum Antiviral Activities against New World Alphaviruses. [Abstract]

2023 Feb 28;15(3):655. PMID: 36992362
Anim Cells Syst

Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells. [Abstract]

2024 May 11;28(1):237-250. PMID: 38741950
Hum Cell

LncRNA OLMALINC promotes osteosarcoma progression through USP1-mediated autophagy suppression. [Abstract]

2025 Apr 18;38(3):91. PMID: 40249458
Cell Press Blue

2026 Jul 3.

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : ≥ 49 mg/mL (127.44 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

* "≥" means soluble, but saturation unknown.

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.6009 mL

13.0046 mL

26.0092 mL

5 mM

0.5202 mL

2.6009 mL

5.2018 mL

10 mM

0.2601 mL

1.3005 mL

2.6009 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (6.50 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (6.50 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (6.50 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protokoll

Kinase Assay^[1]

For DUB profiling, ML-323 is tested at a single-dose of 10 μM in duplicate. The DUB activities are monitored using Ub-7-amido-4-methylcoumarin (AMC) as a substrate. The increase in fluorescent signal from free AMC is monitored over time, although only the initial linear portion of slope (signal/min) is used for analysis. The activity of enzyme with no compound is treated as 100%. For protease profiling, ML-323 is tested using threefold serial dilutions starting at 20 μM against 70 proteases. Proteases are pre-incubated with the compound for 5-15 min before the addition of the appropriate enzyme substrates. The enzyme activities are measured by reading the fluorescent signal from fluorescently labeled peptides^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay^[1]

Cell viability is measured by a cell counting kit (CCK) assay using CCK-8 solution. For the colony-forming assay, cells are seeded at a density of 300-500 cells per well in six-well plates and grown overnight. Cells are then treated with ML-323 alone, Cisplatin alone or a combination of Cisplatin and ML-323 (1:1 or 1:4) at the indicated concentrations. Cells treated with an equal volume of DMSO and saline are used as a control. After 48 h of treatment, fresh growth medium is added, and cells are incubated for an additional 5-10 d to allow for colony formation. For UV combination treatment, the cells are treated with ML-323 at the indicated concentrations or an equal volume of DMSO. After 48 h, the medium is removed, and cells are irradiated at 254 nm at the indicated dosage. Fresh growth medium is added, and the cells are incubated for an additional 5-10 d to allow for colony formation. The cells without UV irradiation but treated with ML-323 or an equal volume of DMSO are used as controls and designated as 100%. After the formation of the colonies, cells are fixed with methanol and stained with 0.5% crystal violet. Colonies consisting of >50 cells are scored. The number of colonies is determined from triplicate plates. The dose-response curves are generated using GraphPad Prism and analyzed by using CalcuSyn to calculate the combination index, which is determined for the fraction of cells affected after the addition of fixed ratios of cisplatin and the USP1-UAF1 inhibitor^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (283 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Liang Q, et al. A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage responses. Nat Chem Biol. 2014 Apr;10(4):298-304. [Content Brief]

[2]. Dexheimer TS, et al. Discovery of ML323 as a Novel Inhibitor of the USP1/UAF1 Deubiquitinase Complex. National Center for Biotechnology Information; 2010-2012 Oct 23. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.6009 mL	13.0046 mL	26.0092 mL	65.0229 mL
	5 mM	0.5202 mL	2.6009 mL	5.2018 mL	13.0046 mL
	10 mM	0.2601 mL	1.3005 mL	2.6009 mL	6.5023 mL
	15 mM	0.1734 mL	0.8670 mL	1.7339 mL	4.3349 mL
	20 mM	0.1300 mL	0.6502 mL	1.3005 mL	3.2511 mL
	25 mM	0.1040 mL	0.5202 mL	1.0404 mL	2.6009 mL
	30 mM	0.0867 mL	0.4335 mL	0.8670 mL	2.1674 mL
	40 mM	0.0650 mL	0.3251 mL	0.6502 mL	1.6256 mL
	50 mM	0.0520 mL	0.2601 mL	0.5202 mL	1.3005 mL
	60 mM	0.0433 mL	0.2167 mL	0.4335 mL	1.0837 mL
	80 mM	0.0325 mL	0.1626 mL	0.3251 mL	0.8128 mL
	100 mM	0.0260 mL	0.1300 mL	0.2601 mL	0.6502 mL

Bioz

Keywords

ML-323

19 Cited Publications

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ML-323

PR-619

P 22077

ML364

P005091

IU1

MF-094

DUB-IN-2

LDN-57444

Degrasyn

SJB3-019A

USP25/28 inhibitor AZ1

EOAI3402143

Publications Citing Use of MedChemExpress (MCE) ML-323

Alle Deubiquitinase Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (19)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Bioz

ML-323

PR-619

P 22077

ML364

P005091

IU1

MF-094

DUB-IN-2

LDN-57444

Degrasyn

SJB3-019A

USP25/28 inhibitor AZ1

EOAI3402143

Publications Citing Use of MedChemExpress (MCE) ML-323

Alle Deubiquitinase Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (19)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

ML-323 Related Classifications

HY-17543 Related Classifications

Bioz