ML385   Click here for help

GtoPdb Ligand ID: 10154

Synonyms: compound 2 [PMID: 27552339] | ML-385
Compound class: Synthetic organic
Comment: ML385 is a small molecule that binds to the Neh1 domain of the NRF2 transcription factor [6]. Activating mutations in NRF2 (and loss-of-function (LOF) mutations in KEAP1, a protein that binds NRF2 and targets it for proteosomal degradation) have been reported to facilitate cytoprotective functions which are associated with mechanisms of chemotherapy resistance and tumour expansion in various solid tumour types [2-5,8-9]. Evidence from preclinical and clinical studies has validated Inhibition of NRF2 as a novel mechanistic therapeutic approach for treatment-resistant tumours [1,7]. ML385 inhibits NRF2 activity in non-small cell lung cancer (NSCLC) cells with LOF KEAP1 mutations in vitro and inhibits tumour growth in xenograft models using KEAP1 mutant NSCLC cells (in combination with carboplatin) [6].

ML385 is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 109
Molecular weight 511.16
XLogP 4.38
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES O=C(Nc1sc(c(n1)c1ccc2c(c1)CCN2C(=O)c1ccccc1C)C)Cc1ccc2c(c1)OCO2
Isomeric SMILES O=C(Nc1sc(c(n1)c1ccc2c(c1)CCN2C(=O)c1ccccc1C)C)Cc1ccc2c(c1)OCO2
InChI 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)
InChI Key LINHYWKZVCNAMQ-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Download 2D Structure Click here for help
Canonical SMILES Download
Isomeric SMILES Download
InChI standard identifier Download
InChI standard key Download

Molecular structure representations generated using Open Babel