ML-210
(Synonyms: DPI10) 目录号 : GC18705ML-210是一种前体药物，能够选择性共价抑制GPX4，EC50值为30nM。
Cas No.:1360705-96-9
Sample solution is provided at 25 µL, 10mM.
ML-210 is a prodrug that selectively inhibits GPX4 covalently with an EC50 of 30nM[1]. ML-210 has been widely used as a target or model compound to develop a range of GPX4 degraders[2].
In vitro, ML-210 treatment at 10μM for 2 hours induced rapid accumulation of lipid radicals in clear-cell renal cell carcinoma cells and caused ferroptosis[3]. Treatment of PANC-1 cells with 3μM ML-210 for 48 hours significantly inhibited cell viability, strongly decreased N-cadherin expression, increased lipid peroxides on the cell membrane, and inhibited cell migration[4]. ML-210 treatment (10μM) for 24h significantly induced cell cycle arrest in ABCB1 overexpressing colorectal cancer cells without altering ABCB1 protein expression[5]. In OCI-AML3 cells, treatment with 0.5µM of ML-210 for 48h simultaneously increased the proportion of annexin V-positive and DAPI-positive cells, resulting in an increased number of apoptotic cells[6].
In vivo, ML-210 treatment (5mg/kg; administered intraperitoneally every other day for 20 days) inhibited ovarian cancer progression and modestly reduced body weight in mice[7].
References:
[1] Eaton J K, Furst L, Ruberto R A, et al. Selective covalent targeting of GPX4 using masked nitrile-oxide electrophiles[J]. Nature chemical biology, 2020, 16(5): 497-506.
[2] Wang H, Wang C, Li B, et al. Discovery of ML210-Based glutathione peroxidase 4 (GPX4) degrader inducing ferroptosis of human cancer cells[J]. European Journal of Medicinal Chemistry, 2023, 254: 115343.
[3] Zou Y, Palte M J, Deik A A, et al. A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis[J]. Nature communications, 2019, 10(1): 1617.
[4] Takemura K, Ikeda K, Miyake H, et al. Epithelial–Mesenchymal Transition Suppression by ML210 Enhances Gemcitabine Anti-Tumor Effects on PDAC Cells[J]. Biomolecules, 2025, 15(1): 70.
[5] Li Y C, Xiong Y M, Long Z P, et al. ML210 Antagonizes ABCB1-Not ABCG2-Mediated Multidrug Resistance in Colorectal Cancer[J]. Biomedicines, 2025, 13(5): 1245.
[6] Akiyama H, Zhao R, Ostermann L B, et al. Mitochondrial regulation of GPX4 inhibition–mediated ferroptosis in acute myeloid leukemia[J]. Leukemia, 2024, 38(4): 729-740.
[7] Li N, Jiang X, Zhang Q, et al. Synergistic suppression of ovarian cancer by combining NRF2 and GPX4 inhibitors: in vitro and in vivo evidence[J]. Journal of Ovarian Research, 2024, 17(1): 49.
ML-210是一种前体药物，能够选择性共价抑制GPX4，EC50值为30nM[1]。ML-210已被广泛用作靶点或模型化合物来开发多种GPX4降解剂[2]。
在体外，10μM浓度的ML-210处理2小时可诱导透明细胞肾癌细胞中脂质自由基的快速积累并引发铁死亡[3]。用3μM浓度的ML-210处理PANC-1细胞48小时能显著抑制细胞活力，明显降低N-钙黏蛋白表达，增加细胞膜上的脂质过氧化物并抑制细胞迁移[4]。10μM浓度的ML-210处理24小时可在不改变ABCB1蛋白表达的情况下，显著诱导ABCB1过表达的结直肠癌细胞发生细胞周期阻滞[5]。在OCI-AML3细胞中，0.5µM浓度的ML-210处理48小时会同时增加膜联蛋白V阳性和DAPI阳性细胞比例，导致凋亡细胞数量上升[6]。
在体内，采用5mg/kg剂量的ML-210隔天腹腔注射给药持续20天，可抑制小鼠卵巢癌进展并轻微降低体重[7]。
| Cell experiment [1]: | |
Cell lines | PANC-1 cells |
Preparation Method | 2×105 PANC-1 cells were seeded in a 6-well dish plates and incubated for 24h. The cells were treated with 0, 0.025, 0.05, 0.1, 0.3μM ML-210 for 24h. The cells were then trypsinized and suspended in FBS (−) medium and seeded into the culture inserts with a filter membrane (8.0µm). The culture inserts were then put on the bottom of the chambers with 750μL of FBS (+) medium. The filter membranes were fixed with cold methanol and stained with crystal violet after 24h of incubation. The cells on the upper surface of filter membranes were wiped away by using a cotton swab and the cells on the lower surface of the membranes were evaluated under a microscope with the imaging system. Each experiment was done in triplicate. |
Reaction Conditions | 0, 0.025, 0.05, 0.1, 0.3μM; 24h |
Applications | ML-210 treatment inhibited the migration of PANC-1 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | 5-week-old female C57BL/6 mice were bred and raised in SPF laboratory at a temperature of 26℃ with free access to water and food. Mice were inoculated with 5×106 ID8-Luc-puro cells by intraperitoneal injection in 200μL PBS. On the seventh day after cell inoculation, mice were treated with 1mg/kg trigonelline, 30mg/kg ML385, 0.5mg/kg clobetasol propionate, 3mg/kg RSL3, 5mg/kg ML-210, and 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline were given as a control. ML-210 was intraperitoneally administered every other day for a total of 10 administrations. Body weight was measured every 5 days. After treatment, mice were injected with pentobarbitone (1mg/mice) and D-luciferin (3mg/mice) in succession, and luminescence signals were observed within 15min using the In-vivo Xtreme live imaging system. Illuminance intensity was normalized and analyzed by the related software. |
Dosage form | 5mg/kg, every other day for 20 days; i.p. |
Applications | ML-210 treatment inhibited the spread of ID8-Luc-puro cells in mice and modestly reduced body weight in mice. |
References: | |
| Cas No. | 1360705-96-9 | SDF | |
| 别名 | DPI10 | ||
| 化学名 | [4-[bis(4-chlorophenyl)methyl]-1-piperazinyl](5-methyl-4-nitro-3-isoxazolyl)-methanone | ||
| Canonical SMILES | ClC1=CC=C(C(C2=CC=C(Cl)C=C2)N3CCN(C(C4=NOC(C)=C4[N+]([O-])=O)=O)CC3)C=C1 | ||
| 分子式 | C22H20Cl2N4O4 | 分子量 | 475.3 |
| 溶解度 | 25mg/mL in DMSO (Need ultrasonic), 10mg/mL in DMF, slightly soluble in ethanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 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。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1039 mL | 10.5197 mL | 21.0393 mL |
| 5 mM | 0.4208 mL | 2.1039 mL | 4.2079 mL |
| 10 mM | 0.2104 mL | 1.052 mL | 2.1039 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
