ML385

Biological Activity

ML385 inihbits the activity of the Nrf2 transcription factor by binding to Neh1, a NC-bZIP domain that allows Nrf2 to heterodimerize with small Maf proteins, blocking NRF2 transcriptional activity. Much research has been done on activating Nrf2 because it induces cytoprotective antioxidant genes. However, some cancer cells may use Nrf2 similarly for their survival. Nrf2 is overexpressed in certain cancers such as non-small cell lung cancer (NSCLC) often due to loss of function mutations in KEAP1, which targets Nrf2 for proteasomal degradation. ML385 was found to have anti-tumor activity with specificity and selectivity for NSCLC cells with KEAP1 mutations.

Product Citations

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  Exp Ther Med. 2022 May;23(5):358.

  Leonurine: A compound with the potential to prevent acute lung injury
  ML385 purchased from AbMole

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  Pharm Biol. 2022 Dec;60(1):638-651.

  In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicity
  ML385 purchased from AbMole

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  Food Research International. 2022 Sep 12.

  N-3 Polyunsaturated Fatty Acids Protect Esophageal Epithelial Cells from Acid Exposure
  ML385 purchased from AbMole

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  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
  ML385 purchased from AbMole

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  Front Immunol. 2022 Feb 4;13:847861.

  Allicin Improves Intestinal Epithelial Barrier Function and Prevents LPS-Induced Barrier Damages of Intestinal Epithelial Cell Monolayers
  ML385 purchased from AbMole

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  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
  ML385 purchased from AbMole

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

  Nrf2-Mediated Ferroptosis Inhibition Exerts a Protective Effect on Acute-on-Chronic Liver Failure
  ML385 purchased from AbMole

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

  Anti-aging effects of Schisandrin C on H2O2-induced HaCaT
  ML385 purchased from AbMole

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  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
  ML385 purchased from AbMole

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  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
  ML385 purchased from AbMole

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  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
  ML385 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Front Oncol (2021). Figure 4. ML-385 (Abmole Bioscience, Houston, TX, USA)
	Method	Cell Migration and Cell Invasion Assays
	Cell Lines	Murine BC cell line 4T1 cells
	Concentrations	0, 5, 10 µM
	Incubation Time	-
	Results	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.

Chemical Information

Molecular Weight	511.59
Formula	C29H25N3O4S
CAS Number	846557-71-9
Solubility (25°C)	DMSO ≥ 30 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

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