ML324   Click here for help

GtoPdb Ligand ID: 9584

Synonyms: ML-324 | MMV1580488
Immunopharmacology Ligand Antimalarial Ligand
Compound class: Synthetic organic
Comment: ML324 is a cell-permeable, small molecule inhibitor of lysine demethylase 4 (KDM4) family of histone modifying enzymes [2]. KDM4 demethylases are responsible for the removal of H3K9 trimethylation marks from histones. The family members exhibit substantial mechanistic redundancy [4]. ML324 demonstrates antiviral activity and is one of the chemotypes included in the Medicines for Malaria Pandemic Response Box (MMV PRB).

The compound also has antimalarial activity. The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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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
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 CDK toolkit. 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 4
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 65.46
Molecular weight 349.18
XLogP 3.27
No. Lipinski's rules broken 0
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.

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Canonical SMILES CN(CCCNC(=O)c1ccc(cc1)c1cc(O)c2c(c1)cccn2)C
Isomeric SMILES CN(CCCNC(=O)c1ccc(cc1)c1cc(O)c2c(c1)cccn2)C
InChI InChI=1S/C21H23N3O2/c1-24(2)12-4-11-23-21(26)16-8-6-15(7-9-16)18-13-17-5-3-10-22-20(17)19(25)14-18/h3,5-10,13-14,25H,4,11-12H2,1-2H3,(H,23,26)
InChI Key QDBVSOZTVKXUES-UHFFFAOYSA-N
References
1. Matthews KA, Senagbe KM, Nötzel C, Gonzales CA, Tong X, Rijo-Ferreira F, Bhanu NV, Miguel-Blanco C, Lafuente-Monasterio MJ, Garcia BA et al.. (2020)
Disruption of the Plasmodium falciparum Life Cycle through Transcriptional Reprogramming by Inhibitors of Jumonji Demethylases.
ACS Infect Dis, 6 (5): 1058-1075. [PMID:32272012]
2. Rai G, Kawamura A, Tumber A, Liang Y, Vogel JL, Arbuckle JH, Rose NR, Dexheimer TS, Foley TL, King ON et al.. (2010)
Discovery of ML324, a JMJD2 demethylase inhibitor with demonstrated antiviral activity.
Probe Reports from the NIH Molecular Libraries Program,. [PMID:24260783]
3. Reader J, van der Watt ME, Taylor D, Le Manach C, Mittal N, Ottilie S, Theron A, Moyo P, Erlank E, Nardini L et al.. (2021)
Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box.
Nat Commun, 12 (1): 269. [PMID:33431834]
4. Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M et al.. (2006)
Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases.
Cell, 125 (3): 467-81. [PMID:16603238]