ML385

生物活性

ML385通过结合Neh1抑制Nrf2转录因子的活性。Neh1是一个nc-bzip结构域，允许Nrf2与小Maf蛋白异质二聚，阻断Nrf2的转录活性。由于Nrf2能诱导细胞保护抗氧化基因，因此对其进行了大量的活化研究。然而，一些癌细胞可能以类似的方式利用Nrf2来生存。Nrf2在某些癌症中过表达，如非小细胞肺癌(NSCLC)，通常是由于KEAP1功能突变丢失，而KEAP1是Nrf2蛋白酶体降解的靶点。ML385对KEAP1突变的NSCLC细胞具有特异性和选择性的抗肿瘤活性。

使用AbMole产品发表的文献

• Int J Biol Sci. 2024 Aug 07.

  The PI3K/Akt-Nrf2 Signaling Pathway and Mitophagy Synergistically Mediate Hydroxytyrosol to Alleviate Intestinal Oxidative Damage

• Front. Pharmacol. 2024 Jun 28; .

  Brozopine ameliorates cognitive impairment via upregulating Nrf2, antioxidation and anti-inflammation activities

• J Biochem Mol Toxicol. 2024 Aug 01;38(8):e23792.

  Ezetimibe ketone protects against renal ischemia–reperfusion injury and attenuates oxidative stress via activation of the Nrf2/HO-1 signaling pathway

• Nat Prod Commun. 2024 Jan.

  Pachymic Acid Alleviates Oxidative Damage of Retinal Cells Induced by Sodium Iodate or Hydrogen Peroxide by Activating the Nrf2/HO-1 Signaling Pathway

• Mol Cell Toxicol. 2024 May.

  Liquiritin alleviates LPS-stimulated podocyte apoptosis and inflammation by activating Nrf2 signaling

• Free Radic Biol Med. 2023 Mar 27;202:46-61.

  Mitochondrial GRIM-19 loss in parietal cells promotes spasmolytic polypeptide-expressing metaplasia through NLR family pyrin domain-containing 3 (NLRP3)-mediated IL-33 activation via a reactive oxygen species (ROS) -NRF2- Heme oxygenase-1(HO-1)–NF–кB axis

• Phytomedicine. 2023 Mar 28.

  15, 16-Dihydrotanshinone I protects against ischemic stroke by inhibiting ferroptosis via the activation of nuclear factor erythroid 2-related factor 2

• Int J Pharm. 2023 Sep 13;645:123389.

  Effective myocardial infarction treatment by targeted accumulation of Sulforaphane using porous magnetic silica nanoparticles

• Int Immunopharmacol. 2023 May 22;120:110282.

  Melatonin attenuates lipopolysaccharide-induced immune dysfunction in dendritic cells

• J Cancer Res Clin Oncol. 2023 Apr 29.

  Apatinib combined with olaparib induces ferroptosis via a p53-dependent manner in ovarian cancer

• PLoS One. 2023 Sep 8;18(9):e0290264.

  Thymidylate synthase promotes esophageal squamous cell carcinoma growth by relieving oxidative stress through activating nuclear factor erythroid 2-related factor 2 expression

• Mol Med Rep. 2023 Nov;28(5):202.

  Acetyl zingerone ameliorates osteoarthritis by inhibiting chondrocyte programmed cell death

• Front Immunol. 2022 Feb 4;13:847861.

  Allicin Improves Intestinal Epithelial Barrier Function and Prevents LPS-Induced Barrier Damages of Intestinal Epithelial Cell Monolayers

• Free Radic Biol Med. 2022 Nov 3;193(Pt 1):459-473.

  Sirtuin 7 mitigates renal ferroptosis, fibrosis and injury in hypertensive mice by facilitating the KLF15/Nrf2 signaling

• Food Res Int. 2022 Sep 12.

  N-3 Polyunsaturated Fatty Acids Protect Esophageal Epithelial Cells from Acid Exposure

• Oxid Med Cell Longev. 2022 Apr 16;2022:4505513.

  Nrf2-Mediated Ferroptosis Inhibition Exerts a Protective Effect on Acute-on-Chronic Liver Failure

• Front Pharmacol. 2022 Jul 18;13:943111.

  (±)-5-bromo-2-(5-fluoro-1-hydroxyamyl) Benzoate Protects Against Oxidative Stress Injury in PC12 Cells Exposed to H 2 O 2 Through Activation of Nrf2 Pathway

• Pharm Biol. 2022 Dec;60(1):638-651.

  In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicity

• Exp Ther Med. 2022 May;23(5):358.

  Leonurine: A compound with the potential to prevent acute lung injury

• Front Oncol. 2021 May 26;11:679816.

  Antidiabetic Agent DPP-4i Facilitates Murine Breast Cancer Metastasis by Oncogenic ROS-NRF2-HO-1 Axis via a Positive NRF2-HO-1 Feedback Loop

• Biomed Res Int. 2021 Jun 10;2021:6616547.

  Antioral Squamous Cell Carcinoma Effects of Carvacrol via Inhibiting Inflammation, Proliferation, and Migration Related to Nrf2/Keap1 Pathway

• Pharmacol Res Perspect. 2021 May;9(3):e00791.

  Dexamethasone promotes the endoplasmic reticulum stress response of bone marrow mesenchymal stem cells by activating the PERK-Nrf2 signaling pathway

• Med J Chin PLA. 2021 Mar 28;Vol. 46, No. 3.

  Anti-aging effects of Schisandrin C on H2O2-induced HaCaT

产品使用成果展示

	数据来源	Front Oncol (2021). Figure 4. ML-385 (Abmole Bioscience, Houston, TX, USA)
	方法	Cell Migration and Cell Invasion Assays
	细胞系/动物模型	Murine BC cell line 4T1 cells
	浓度	0, 5, 10 µM
	处理时间	-
	实验结果	We found that ML-385 treatment significantly attenuated NRF2, p-NRF2 expression (Figure 4A) and NRF2-responsive gene levels (Figure 4B) in DPP-4i-treated BC cells. Notably, DPP-4i-driven BC cell migration and invasion were significantly abrogated by ML-385 treatment with a dose-dependent manner (Figures 4C, D). Furthermore, DPP-4i–driven metastasis-associated gene levels were significantly attenuated after ML-385 treatment in BC cells (Figure 4E). These data indicate that NRF2 inhibition reverses DPP-4i–driven BC metastases in vitro.

化学性质

分子量	511.59
分子式	C29H25N3O4S
CAS号	846557-71-9
溶解性（25°C）	DMSO ≥ 25 mg/mL
储存条件	粉末型式       -20°C   3年；4°C   2年 溶于溶剂       -80°C   6个月；-20°C   1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.9547 mL	9.7735 mL	19.5469 mL
5 mM	0.3909 mL	1.9547 mL	3.9094 mL
10 mM	0.1955 mL	0.9773 mL	1.9547 mL

溶液配置摩尔浓度计算器

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] Anju Singh, et al. ACS Chem Biol. Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors