Synonym
ML-385; ML 385; ML385.
IUPAC/Chemical Name
N-[4-[2,3-dihydro-1-(2-methylbenzoyl)-1H-indol-5-yl]-5-methyl-2-thiazolyl]-1,3-benzodioxole-5-acetamide
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)
SMILES Code
O=C(NC1=NC(C2=CC3=C(N(C(C4=CC=CC=C4C)=O)CC3)C=C2)=C(C)S1)CC5=CC=C(OCO6)C6=C5
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
ML385 is a nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor with an IC50 of 1.9 μM.
In vitro activity:
To determine whether the interaction between NRF2 and ML385 inhibits NRF2-mediated transcription, A549 cells were cultured in the presence of ML385 for 72 h and the changes in the expression levels of NRF2 and its target genes were measured. As shown in Figure 4a, a dose-dependent reduction in the NRF2 transcriptional activity was detected and the maximum inhibitory concentration was 5 μM ML385. To determine the time-dependent kinetics of this effect, A549 cells were treated with ML385 (5 μM) and the expression of the antioxidant target genes was measured at various time points. Again, there was a time-dependent decrease in NRF2 signaling and the maximum decline was at 72 h (Figure 4b). In addition to reducing mRNA levels of NRF2 target genes, a reduction in NRF2 mRNA levels was also observed.
Reference: ACS Chem Biol. 2016 Nov 18;11(11):3214-3225. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367156/
In vivo activity:
The therapeutic efficacy of ML385 was evaluated in orthotopic models of human NSCLC (non-small cell lung cancer) that closely recapitulate clinical patterns of lung cancer progression. A single tumor was established within the left or right lung of mice. In the A549 lung cancer orthotopic model, mice treated with vehicle had 34% lung volume at 3 weeks compared to their pre-treatment volume. The ML385-treated group had 57% of their pretreatment lung volume at 3 weeks (Figure 7a). These results indicate that ML385 therapy blocks orthotopic human lung tumor growth.
Reference: ACS Chem Biol. 2016 Nov 18;11(11):3214-3225. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367156/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
31.4 |
61.38 |
|
| DMF |
30.0 |
58.64 |
|
| DMF:PBS (pH 7.2) (1:3) |
0.3 |
0.49 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
511.60
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Singh A, Venkannagari S, Oh KH, Zhang YQ, Rohde JM, Liu L, Nimmagadda S, Sudini K, Brimacombe KR, Gajghate S, Ma J, Wang A, Xu X, Shahane SA, Xia M, Woo J, Mensah GA, Wang Z, Ferrer M, Gabrielson E, Li Z, Rastinejad F, Shen M, Boxer MB, Biswal S. Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors. ACS Chem Biol. 2016 Nov 18;11(11):3214-3225. doi: 10.1021/acschembio.6b00651. Epub 2016 Oct 17. PMID: 27552339; PMCID: PMC5367156.
In vitro protocol:
1. Singh A, Venkannagari S, Oh KH, Zhang YQ, Rohde JM, Liu L, Nimmagadda S, Sudini K, Brimacombe KR, Gajghate S, Ma J, Wang A, Xu X, Shahane SA, Xia M, Woo J, Mensah GA, Wang Z, Ferrer M, Gabrielson E, Li Z, Rastinejad F, Shen M, Boxer MB, Biswal S. Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors. ACS Chem Biol. 2016 Nov 18;11(11):3214-3225. doi: 10.1021/acschembio.6b00651. Epub 2016 Oct 17. PMID: 27552339; PMCID: PMC5367156.
In vivo protocol:
1. Singh A, Venkannagari S, Oh KH, Zhang YQ, Rohde JM, Liu L, Nimmagadda S, Sudini K, Brimacombe KR, Gajghate S, Ma J, Wang A, Xu X, Shahane SA, Xia M, Woo J, Mensah GA, Wang Z, Ferrer M, Gabrielson E, Li Z, Rastinejad F, Shen M, Boxer MB, Biswal S. Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors. ACS Chem Biol. 2016 Nov 18;11(11):3214-3225. doi: 10.1021/acschembio.6b00651. Epub 2016 Oct 17. PMID: 27552339; PMCID: PMC5367156.
1: Singh A, Venkannagari S, Oh KH, Zhang YQ, Rohde JM, Liu L, Nimmagadda S,
Sudini K, Brimacombe KR, Gajghate S, Ma J, Wang A, Xu X, Shahane SA, Xia M, Woo
J, Mensah GA, Wang Z, Ferrer M, Gabrielson E, Li Z, Rastinejad F, Shen M, Boxer
MB, Biswal S. Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic
Resistance in KEAP1-Deficient NSCLC Tumors. ACS Chem Biol. 2016 Nov
18;11(11):3214-3225. Epub 2016 Oct 17. PubMed PMID: 27552339; PubMed Central
PMCID: PMC5367156.
