ML323

製品コードS7529 バッチS752902

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H24N6
分子量 384.48 CAS No. 1572414-83-5
Solubility (25°C)* 体外 DMSO 76 mg/mL (197.66 mM)
Ethanol 38 mg/mL (98.83 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 ML323 displays reversible, nanomolar inhibitory activity and excellent selectivity toward USP1/UAF1 with IC50 of 76 nM.
in vitro

ML323 inhibits the deubiquitination of PCNA and FANCD2 by inhibiting USP1–UAF1 activity in H596 cells. Moreover, this compound potentiates cytotoxicity in NSCLC H596 cells and U2OS osteosarcoma cells by targeting two major DNA damage response pathways (TLS and FA). [1]
in vivo

This compound is a selective USP1–UAF1 inhibitor that inhibit deubiquitinase activity of USP1–UAF1 complex.
特徴 USP1-UAF1-selective inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ High-throughput screening
For HTS, USP1-UAF1 activity is monitored using ubiquitin-rhodamine 110 as a substrate. The assay is miniaturized to a 4 μL volume in a 1,536-well format and is used to screen approximately 402,701 compounds in quantitative HTS mode, with each compound tested over a range of four to five concentrations. The assay shows robust performance with an average Z’factor of 0.8 throughout the screen.
細胞アッセイ 細胞株 H596 cells
濃度 ~30 μM
反応時間 7-12 days
実験の流れ

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 ML323 alone at the indicated concentrations. Cells treated with an equal volume of DMSO and saline are used as 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 this compound 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 this chemical 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.
動物実験 動物モデル Female C57BL/6J mice
投薬量 10 mg/kg
投与方法 i.p.

参考

  • https://pubmed.ncbi.nlm.nih.gov/24531842/
  • https://pubmed.ncbi.nlm.nih.gov/29138248/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Survivin Is a Central Mediator of Cell Proliferation in HPV-Negative Head and Neck Squamous Cell Carcinoma [ Cancers (Basel), 2025, 17(17)2864] PubMed: 40940964
Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer [ Oncol Res, 2025, 33(1):213-224] PubMed: 39735674
Polyubiquitinated PCNA triggers SLX4-mediated break-induced replication in alternative lengthening of telomeres (ALT) cancer cells [ Nucleic Acids Res, 2024, gkae785] PubMed: 39291733
Multi-regulatory potency of USP1 on inflammasome components promotes pyroptosis in thyroid follicular cells and contributes to the progression of Hashimoto's thyroiditis [ Mol Med, 2024, 30(1):121] PubMed: 39134949
USP1 promotes the aerobic glycolysis and progression of T-cell acute lymphoblastic leukemia via PLK1/LDHA axis [ Blood Adv, 2023, 7(13):3099-3112] PubMed: 36912760
PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity [ PLoS One, 2023, 18(5):e0285337] PubMed: 37205694
The Deubiquitinating Enzyme USP1 is Auto-Ubiquitinated and Destabilized by ML323 in Colorectal Cancer Cells [ Eurasian J Med Oncol, 2023, 7(2):174–179] PubMed: none
USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells [ J Exp Clin Cancer Res, 2021, 40(1):201] PubMed: 34154657
A new role of GRP75-USP1-SIX1 protein complex in driving prostate cancer progression and castration resistance [ Oncogene, 2021, 40(25):4291-4306] PubMed: 34079090
Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization [ Front Pharmacol, 2021, 12:695009] PubMed: 34149436

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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