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ML-323 Sale

目录号 : GC17635

A selective USP1-UAF1 deubiquitinase complex inhibitor

ML-323 Chemical Structure

Cas No.:1572414-83-5

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥567.00
现货
5mg
¥473.00
现货
25mg
¥2,069.00
现货

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Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

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实验参考方法

Kinase experiment:

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].

Cell experiment:

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].

References:

[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.
[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.

产品描述

IC50: ML-323 is a highly potent and selective inhibitor of USP1-UAF1 with IC50 value of 76 nM.

ML-323 is an inhibitor of USP1-UAF1 with remarkable selectivity and relatively low cytotoxicity to the human cells. [1] USP1-UAF1 is closely linked to the DNA damage response and is recently suggested as a strategy for overcoming drug resistance during antitumor therapy. [1]

In vitro: Studies in H596 cells showed that ML-323 blocked the deubiquitination of PCNA and FANCD2 via suppressing USP1–UAF1 activity. It was reported that ML-323 potently inhibited USP1-UAF1 with IC50 values of 76 nM and 174 nM in ubiquitin-rhodamine (Ub-Rho) assay and orthogonal gel-based assay, respectively. In addition, by targeting TLS and FA, two major DNA damage response pathways, ML-323 increased cisplatin cytotoxicity both in NSCLC H596 cells and U2OS osteosarcoma cells. Moreover, this agent exhibited a high selectivity to human DUBs, deSUMOylase, deneddylase and unrelated proteases. [1]

In vivo: So far, no in vivo study has been conducted.

Clinical trial: So far, no clinical trial has been conducted.

Reference:
[1]Liang Q, Dexheimer TS, Zhang P, Rosenthal AS, Villamil MA, You C, Zhang Q, Chen J, Ott CA, Sun H, Luci DK, Yuan B, Simeonov A, Jadhav A, Xiao H, Wang Y, Maloney DJ and Zhuang Z.  A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage responses. Nat Chem Biol. 2014 April; 10(4): 298–304.

Chemical Properties

Cas No. 1572414-83-5 SDF
化学名 (E)-1-(4-(1H-1,2,3-triazol-1-yl)phenyl)-N-(2-(2-isopropylphenyl)-5-methylpyrimidin-4(3H)-ylidene)methanamine
Canonical SMILES CC(C1=CC=CC=C1C2=NC=C(/C(N2)=N\CC3=CC=C(N4C=CN=N4)C=C3)C)C
分子式 C23H24N6 分子量 384.48
溶解度 ≥ 15.05mg/mL in DMSO 储存条件 Store at -20°C
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储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
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溶解性数据

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1 mg 5 mg 10 mg
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
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