darizmetinib   Click here for help

GtoPdb Ligand ID: 12376

Synonyms: example 63 [WO2019149738A1]
Compound class: Synthetic organic
Comment: This is the chemical structure for the INN darizmetinib. This structure is claimed in HepaRegeniX's patent WO2019149738A1, as a mitogen-activated protein kinase kinase 4 (MKK4) inhibitor [1]. We suspect that darizmetinib is HepaRegeniX's lead MKK4 inhibitor HRX-0215, that has entered phase 1 clinical trial, although name>structure for HRX-0215 has not been formally disclosed (Feb 2023). MKK4 is a key regulator of liver regeneration. Inhibition of MKK4 promotes the regenerative capacity of hepatocytes.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

darizmetinib 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 7
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 126.08
Molecular weight 457.1
XLogP 3.83
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 CCCS(=O)(=O)Nc1c(F)ccc(c1F)C(=O)c1[nH]nc2c1cc(cn2)c1ccncc1
Isomeric SMILES CCCS(=O)(=O)Nc1c(ccc(c1F)C(=O)c1c2cc(cnc2n[nH]1)c1ccncc1)F
InChI InChI=1S/C21H17F2N5O3S/c1-2-9-32(30,31)28-19-16(22)4-3-14(17(19)23)20(29)18-15-10-13(11-25-21(15)27-26-18)12-5-7-24-8-6-12/h3-8,10-11,28H,2,9H2,1H3,(H,25,26,27)
InChI Key WBNMARNYIFMNEP-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/)
No information available.
Summary of Clinical Use Click here for help
The MKK4 inhibitor HRX-0215 has entered phase 1, first-in-human evaluation (August 2021). It will be tested for efficacy as a treatment for acute and chronic liver diseases.