ML385

Alias: ML385; ML 385; ML-385
Cat No.:V2828 Purity: ≥98%
ML-385 is a novel, potent and selective NRF2 inhibitor (Nrf2: nuclear factor E2 related factor 2) with an IC50 of 1.9 µM.
ML385 Chemical Structure CAS No.: 846557-71-9
Product category: Keap1-Nrf2
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: =100%

Purity: =100%

Purity: ≥98%

Product Description
ML-385 is a novel, potent and selective NRF2 inhibitor (Nrf2: nuclear factor E2 related factor 2) with an IC50 of 1.9 µM. NRF2 and ML385 interact, which changes the NRF2-MAFG protein complex's capacity to bind DNA. Anisotropy is reduced dose-dependently by ML385 addition. In KEAP1-Deficient NSCLC Tumors, ML-385 targets therapeutic resistance with precision. It works by preventing NRF2's downstream target gene expression. The combination of ML385 and chemotherapeutic drugs like carboplatin demonstrated significant tumor-suppressive activity.
Biological Activity I Assay Protocols (From Reference)
Targets
NRF2 (IC50 = 1.9 μM)
ln Vitro
ML385 exhibits anti-tumor activity in NSCLC (subcutaneous and orthotopic NSCLC models) both as a single agent and in combination with carboplatin. ML385 has a half-life (t1/2 = 2.82 h) after IP injection (30 mg/kg), according to the PK profile examined in CD-1 mice[1]. The pancreatic injury might be reduced by ML385[2].
ln Vivo
ML385 in combination with DNA alkylating agent carboplatin leads to a significant reduction in tumor cell proliferation, as demonstrated by fewer Ki-67 positive cells. NRF2 protein levels and its downstream target genes are significantly decreased in tumor samples treated with ML385.
Animal Protocol
8-week-old C57B/6 male mice
30 mg/kg; 7 days
Intraperitoneal injection
References

[1]. ACS Chem Biol . 2016 Nov 18;11(11):3214-3225.

[2]. Isoliquiritigenin Ameliorates Acute Pancreatitis in Mice via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway.

[3]. Respir Res . 2020 Sep 9;21(1):232.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C29H25N3O4S
Molecular Weight
511.60
Exact Mass
511.16
Elemental Analysis
C, 68.08; H, 4.93; N, 8.21; O, 12.51; S, 6.27
CAS #
846557-71-9
Related CAS #
846557-71-9
Appearance
Solid powder
SMILES
CC1=CC=CC=C1C(=O)N2CCC3=C2C=CC(=C3)C4=C(SC(=N4)NC(=O)CC5=CC6=C(C=C5)OCO6)C
InChi Key
LINHYWKZVCNAMQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C29H25N3O4S/c1-17-5-3-4-6-22(17)28(34)32-12-11-20-15-21(8-9-23(20)32)27-18(2)37-29(31-27)30-26(33)14-19-7-10-24-25(13-19)36-16-35-24/h3-10,13,15H,11-12,14,16H2,1-2H3,(H,30,31,33)
Chemical Name
2-(1,3-benzodioxol-5-yl)-N-[5-methyl-4-[1-(2-methylbenzoyl)-2,3-dihydroindol-5-yl]-1,3-thiazol-2-yl]acetamide
Synonyms
ML385; ML 385; ML-385
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ≥ 30 mg/mL
Water: N/A
Ethanol: N/A
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 2: ≥ 2.08 mg/mL (4.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: 6% DMSO+40% PEG 300+5%Tween80+ 49%ddH2O: 1.5mg/ml


Solubility in Formulation 4: 10 mg/mL (19.55 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 5: 9.01 mg/mL (17.61 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 6: 5 mg/mL (9.77 mM) in 15% Solutol HS 15 10% Cremophor EL 35% PEG 400 40% water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.9547 mL 9.7733 mL 19.5465 mL
5 mM 0.3909 mL 1.9547 mL 3.9093 mL
10 mM 0.1955 mL 0.9773 mL 1.9547 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Biological Data
  • ML385

    Figure 4 ML385 inhibits NRF2 signaling in lung cancer cells.2016 Nov 18;11(11):3214-3225. Epub 2016 Oct 17.
  • ML385

    ML385 directly interacts with purified NRF2 protein.2016 Nov 18;11(11):3214-3225. Epub 2016 Oct 17.

  • ML385

    ML385 is selectively toxic to cells with KEAP1 mutations and potentiates the toxicity of chemotherapy drugs in NSCLC cells with KEAP1 mutations.2016 Nov 18;11(11):3214-3225. Epub 2016 Oct 17.
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